Between 1940 and 1970 pioneers in the new field of cell biology discovered the operative parts of cells and their contributions to cell life. They offered mechanistic accounts that explained cellular phenomena by identifying the relevant parts of cells, the biochemical operations they performed, and the way in which these parts and operations were organised to accomplish important functions. Cell biology was a revolutionary science but in this book it also provides fuel for yet another revolution, one (...) that focuses on the very conception of science itself. Laws have traditionally been regarded as the primary vehicle of explanation, but in the emerging philosophy of science it is mechanisms that do the explanatory work. Bechtel emphasises how mechanisms were discovered, focusing especially on the way in which new instruments made these inquiries possible. He also describes how new journals and societies provided institutional structure to this new enterprise. (shrink)

The ‘universal cell reaction’ (UCR), a coordinated biphasic response to external (noxious and other) stimuli observed in all living cells, was described by Nasonov and his colleagues in the mid‐20th century. This work has received no attention from cell biologists in the West, but the UCR merits serious consideration. Although it is non‐specific, it is likely to be underpinned by precise mechanisms and, if these mechanisms were characterized and their relationship to the UCR elucidated, then our understanding of (...) the integration of cellular function could be improved. As a step towards identifying such mechanisms, I review some recent advances in understanding cell mechanics and the stress response and I suggest potentially testable hypotheses. There is a particular need for time‐course studies of cellular responses to different stimulus doses or intensities. I also suggest a correspondence with hormesis; re‐investigation of the UCR using modern biophysical and molecular‐biological techniques might throw light on this much‐discussed phenomenon. BioEssays 29:324–333, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Between 1940 and 1970 pioneers in the new field of cell biology discovered the operative parts of cells and their contributions to cell life. They offered mechanistic accounts that explained cellular phenomena by identifying the relevant parts of cells, the biochemical operations they performed, and the way in which these parts and operations were organised to accomplish important functions. Cell biology was a revolutionary science but in this book it also provides fuel for yet another revolution, one (...) that focuses on the very conception of science itself. Laws have traditionally been regarded as the primary vehicle of explanation, but in the emerging philosophy of science it is mechanisms that do the explanatory work. Bechtel emphasises how mechanisms were discovered, focusing especially on the way in which new instruments made these inquiries possible. He also describes how new journals and societies provided institutional structure to this new enterprise. (shrink)

Despite its uniform appearance, the cerebellar cortex is highly heterogeneous in terms of structure, genetics and physiology. Purkinje cells (PCs), the principal and sole output neurons of the cerebellar cortex, can be categorized into multiple populations that differentially express molecular markers and display distinctive physiological features. Such features include action potential rate, but also their propensity for synaptic and intrinsic plasticity. However, the precise molecular and genetic factors that correlate with the differential physiological properties of PCs remain elusive. In this (...) article, we provide a detailed overview of the cellular mechanisms that regulate PC activity and plasticity. We further perform a pathway analysis to highlight how molecular characteristics of specific PC populations may influence their physiology and plasticity mechanisms. (shrink)

How Darwin's “endless forms most beautiful” have evolved remains one of the most exciting questions in biology. The significant variety of bacterial shapes is most likely due to the specific advantages they confer with respect to the diverse environments they occupy. While our understanding of the mechanisms generating relatively simple shapes has improved tremendously in the last few years, the molecular mechanisms underlying the generation of complex shapes and the evolution of shape diversity are largely unknown. The emerging field of (...) bacterial evolutionary cell biology provides a novel strategy to answer this question in a comparative phylogenetic framework. This relatively novel approach provides hypotheses and insights into cell biological mechanisms, such as morphogenesis, and their evolution that would have been difficult to obtain by studying only model organisms. We discuss the necessary steps, challenges, and impact of integrating “evolutionary thinking” into bacterial cell biology in the genomic era. (shrink)

The developmental programs of eukaryotic organisms involve the programmed transcription of genes. A characteristic gene expression pattern is established and preserved in each different cell type. Therefore, gene activation at a particular time and its maintenance during cell division are significant for cellular differentiation and individual development. Although many studies have sought to explain the molecular mechanisms of gene expression regulation, the mechanism through which gene expression states are inherited during cell division has not been fully elucidated (...) yet. This review illustrates the general principles and the complexities involved in the establishment and maintenance of active transcription through cell cycles. It focuses on the most‐recent findings about the ways in which molecular memory marks for active transcription are coordinated with cell cycle events, such as replication, mitosis and nuclear organization, to mediate transcription memory across cell division events, which may establish a unifying memory process of active transcription. BioEssays 27:1239–1245, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Actomyosin (actin‐myosin II complex)‐mediated contractile forces are central to the generation of multifaceted uni‐ and multi‐cellular material properties and dynamics such as cell division, migration, and tissue morphogenesis. In the present article, we summarize our recent researches addressing molecular mechanisms that ensure actomyosin‐mediated directional cell–cell junction remodeling, either shortening or extension, driving cell rearrangement for epithelial morphogenesis. Genetic perturbation clarified two points concerning cell–cell junction remodeling: an inhibitory mechanism against negative feedback in which actomyosin (...) contractile forces, which are well known to induce cell–cell junction shortening, can concomitantly alter actin dynamics, oppositely leading to perturbation of the shortening; and tricellular junctions as a point that organizes extension of new cell–cell junctions after shortening. These findings highlight the notion that cells develop underpinning mechanisms to transform the multi‐tasking property of actomyosin contractile forces into specific and proper cellular dynamics in space and time. (shrink)

Developing models of biological mechanisms, such as those involved in respiration in cells, often requires collaborative effort drawing upon techniques developed and information generated in different disciplines. Biochemists in the early decades of the 20th century uncovered all but the most elusive chemical operations involved in cellular respiration, but were unable to align the reaction pathways with particular structures in the cell. During the period 1940-1965 cell biology was emerging as a new discipline and made distinctive contributions to (...) understanding the role of the mitochondrion and its component parts in cellular respiration. In particular, by developing techniques for localizing enzymes or enzyme systems in specific cellular components, cell biologists provided crucial information about the organized structures in which the biochemical reactions occurred. Although the idea that biochemical operations are intimately related to and depend on cell structures was at odds with the then-dominant emphasis on systems of soluble enzymes in biochemistry, a reconceptualization of energetic processes in the 1960s and 1970s made it clear why cell structure was critical to the biochemical account. This paper examines how numerous excursions between biochemistry and cell biology contributed a new understanding of the mechanism of cellular respiration. (shrink)

The chromosomes undergo a condensation‐decondensation cycle within the life cycle of mammalian cells. Chromosome condensation is a complex and critical event that is necessary for the equal distribution of genetic material between the two daughter cells. Although chromosome condensation‐decondensation and segregation is mechanistically complex, it proceeds with high fidelity during the eukaryotic cell division cycle. Cell fusion studies have indicated the presence of chromosome condensation factors in mammalian cells during mitosis. If extracts from mitotic cells are injected into (...) immature oocytes of Xenopus laevis, they induce meiotic maturation (i.e. germinal vesicle breakdown and chromosome condensation) within 2–3 hours. Recently, we showed that the maturation‐promoting activity of the mitotic cell extracts is inactivated by certain protein factors present in cells during the G1 period. The activity of the G1 factors coincides with the process of chromosome decondensation that begins at telophase and continues throughout the G1 period. These studies have revealed that the mitotic factors and the G1 factors play a pivotal role in the regulation of condensation and decondensation of chromosomes. Furthermore, our studies strongly suggest that nonhistone protein phosphorylation and dephosphorylation may mediate chromosome condensation and decondensation, respectively. (shrink)

The differentiation of male and female characteristics in vertebrates and insects has long been thought to proceed via different mechanisms. Traditionally, vertebrate sexual development was thought to occur in two phases: a primary and a secondary phase, the primary phase involving the differentiation of the gonads, and the secondary phase involving the differentiation of other sexual traits via the influence of sex hormones secreted by the gonads. In contrast, insect sexual development was thought to depend exclusively on cell‐autonomous expression (...) of sex‐specific genes. Recently, however, new evidence indicates that both vertebrates and insects rely on sex hormones as well as cell‐autonomous mechanisms to develop sexual traits. Collectively, these new data challenge the traditional vertebrate definitions of primary and secondary sexual development, call for a redefinition of these terms, and indicate the need for research aimed at explaining the relative dependence on cell‐autonomous versus hormonally guided sexual development in animals. (shrink)

The cell theory of Schleiden and Schwann is generalized to the effect that throughout the natural world, in physics, biology, and sociopsychology, there is a widespread phenomenon of the existence of organized cells, whose organization is usually protected by barriers. These barriers exist not only in space, but in time and even in other domains. These barriers typically not only protect the organization within the cell from external disturbance, but they actively participate in reducing the internal disorganization. It (...) appears that the quantum phase cell or its equivalent, the discrete quantum state, may be a physical analog of the organized biological cell. The sampling and ambiguity theorems of communication theory throw new light on phase cells. The quantum phase cell has both configuration and momentum elements, which are analogous respectively to the somatic elements in the cytoplasm of a cell and the genetic elements in the DNA. A biological cell or organism, a physical quantum state, and a human being as a sociopsychological entity each has a natural individuality. A natural individuality is a somewhat mysterious thing, since in addition to specificity, it also involves stochasticity and complementarity. There are some striking and unexplained spin-analog characteristics in biology which have a relation to boson- and fermion-analog characteristics in biology that corresponds with the known relation in physics. The hypothesis suggested in our earlier paper, that quantum mechanical entropy is diminished in interaction, is clarified and sharpened in this paper. (shrink)

Transcriptional networks regulate cell fate decisions, which occur at the level of individual cells. However, much of what we know about their structure and function comes from studies averaging measurements over large populations of cells, many of which are functionally heterogeneous. Such studies conceal the variability between cells and so prevent us from determining the nature of heterogeneity at the molecular level. In recent years, many protocols and platforms have been developed that allow the high throughput analysis of gene (...) expression in single cells, opening the door to a new era of biology. Here, we discuss the need for single cell gene expression analysis to gain deeper insights into the transcriptional control of cell fate decisions, and consider the insights it has provided so far into transcriptional regulatory networks in development. (shrink)

Plant cell culture systems have become an attractive and sustainable approach to produce high‐value and commercially significant metabolites under controlled conditions. Strategies involving elicitor supplementation into plant cell culture media are employed to mimic natural conditions for increasing the metabolite yield. Studies on nanoparticles (NPs) that have investigated elicitation of specialized metabolism have shown the potential of NPs to be a substitute for biotic elicitors such as phytohormones and microbial extracts. Customizable physicochemical characteristics allow the design of monodispersed‐, (...) stimulus‐responsive‐, and hormone‐carrying‐NPs of precise geometries to enhance their elicitation capabilities based on target metabolite/plant cell culture type. We contextualize advances in NP‐mediated elicitation, especially stimulation of specialized metabolic pathways, the underlying mechanisms, impacts on gene regulation, and NP‐associated cytotoxicity. The novelty of the concept lies in unleashing the potential of designer NPs to enhance yield, harness metabolites, and transform nanoelicitation from exploratory investigations to a commercially viable strategy. (shrink)

Secretion is a fundamental cellular process involving the regulated release of intracellular products from cells. Physiological functions such as neurotransmission, or the release of hormones and digestive enzymes, are all governed by cell secretion. Anomalies in the processes involved in secretion contribute to the development and progression of diseases such as diabetes and other hormonal disorders. To unravel the mechanisms that govern such diseases, it is essential to understand how hormones, growth factors and neurotransmitters are synthesized and processed, and (...) how their signals are recognized, amplified and transmitted by intracellular signaling pathways in the target cells. Here, we discuss diverse aspects of the detailed mechanisms involved in secretion based on mathematical models. The models range from stochastic ones describing the trafficking of secretory vesicles to deterministic ones investigating the regulation of cellular processes that underlie hormonal secretion. In all cases, the models are closely related to experimental results and suggest theoretical predictions for the secretion mechanisms. (shrink)

During morphogenesis, tissues undergo extensive remodeling to get their final shape. Such precise sculpting requires the application of forces generated within cells by the cytoskeleton and transmission of these forces through adhesion molecules within and between neighboring cells. Within individual cells, microtubules together with actomyosin filaments and intermediate filaments form the composite cytoskeleton that controls cell mechanics during tissue rearrangements. While studies have established the importance of actin‐based mechanical forces that are coupled via intercellular junctions, relatively little is (...) known about the contribution of other cytoskeletal components such as microtubules to cell mechanics during morphogenesis. In this review the focus is on recent findings, highlighting the direct mechanical role of microtubules beyond its well‐established role in trafficking and signaling during tissue formation. (shrink)

This paper examines the notion of the biopolitical body from the standpoint of Foucault’s logic of the security mechanism and the history he tells of vaccine technology. It then investigates how the increasing importance of the genetic code for determining the meaning and limits of the human in the field of 20th century cell biology has been a cause for ongoing transformation in the practices that currently extend vaccine research and development. I argue that these transformations mark the emergence (...) of a new kind of medical subject – the stabilized and infinitely reproducible human cell line – and that the practices and markets exploiting this new form of organism have had a destabilizing effect on the very biopolitical structures that engendered them and, in fact, mark a new way of conceiving the possibilities of cellular life. I call these new ways of organizing power that intervene in the logic of the security measure by mediating the relationship between populations and persons the microbiopolitical. (shrink)

Graphical AbstractA cell translocation mechanism displaces sporadic mutant cells from normal, suppressive epithelial environment during early steps of tumor initiation. This epithelial cell translocation process exerts a selective pressure on early mutant cells to survive and grow in new microenvironment outside of their native niches.

Cell membranes experience frequent stretching and poking: from cytoskeletal elements, from osmotic imbalances, from fusion and budding of vesicles, and from forces from the outside. Are the ensuing changes in membrane tension localized near the site of perturbation, or do these changes propagate rapidly through the membrane to distant parts of the cell, perhaps as a mechanical mechanism of long‐range signaling? Literature statements on the timescale for membrane tension to equilibrate across a cell vary by a factor (...) of ≈106. This study reviews and discusses how apparently contradictory findings on tension propagation in cells can be evaluated in the context of 2D hydrodynamics and poroelasticity. Localization of tension in the cell membrane is likely critical in governing how membrane forces gate ion channels, set the subcellular distribution of vesicle fusion, and regulate the dynamics of cytoskeletal growth. Furthermore, in this study, it is proposed that cells can actively regulate the degree to which membrane tension propagates by modulating the density and arrangement of immobile transmembrane proteins. Also see the video abstract here https://youtu.be/T6K7AIAqqBs. (shrink)

The mode and timing of germ-cell specification has been studied in diverse organisms, however, the molecular mechanism regulating germ-cell-fate determination remains to be elucidated. In some model organisms, maternal germ-cell determinants play a key role. In mouse embryos, some germ-line-specific gene products exist as maternal molecules and play critical roles in a pluripotential cell population at preimplantation stages. From those cells, primordial germ cells (PGCs) are specified by extracellular signaling mediated by tissue, as well as (...) class='Hi'>cell–cell interaction during gastrulation. Thus, establishment of germ-cell lineage in mammalian embryos appears to be regulated by a multistep process, including formation and maintenance of a pluripotential cell population, as well as specification of PGCs. PGCs can be generated from pluripotential embryonic stem (ES) cells in a simple monolayer culture in which tissue interaction does not occur. This raises the possibility that ES cells, as well as, possibly, pluripotential cells in preimplantation embryos, are more closely related to the PGC precursors than pluripotential cells after implantation. BioEssays 27:136–143, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Neural crest cells are remarkable in their extensive and stereotypic patterns of migration. The pathways of neural crest migration have been documented by cell marking techniques, including interspecific neural tube grafts, immunocytochemistry and Dil‐labelling. In the trunk, neural crest cells migrate dorsally under the skin or ventrally through the somites, where they move in a segmental fashion through the rostral half of each sclerotome. The segmental migration of neural crest cells appears to be prescribed by the somites, perhaps by (...) an inhibitory cue from the caudal half. Within the rostral sclerotome, neural crest cells fill the available space except for a region around the notochord, suggesting the notochord may inhibit neural crest cells in its vicinity. In the cranial region, antibody perturbation experiments suggest that multiple cell‐matrix interactions are required for proper in vivo migration of neural crest cells. Neural crest cells utilize integrin receptors to bind to a number of extracellular matrix molecules. Substrate selective inhibition of neural crest cell attachment in vitro by integrin antibodies and antisense oligonucleotides has demonstrated that they possess at least three integrins, one being an α1β1 integrin which functions in the absence of divalent cations. Thus, neural crest cells utilize complex sets of interactions which may differ at different axial levels. (shrink)

Bidirectional trans‐synaptic signaling is essential for the formation, maturation, and plasticity of synaptic connections. Synaptic cell adhesion molecules (CAMs) are prime drivers in shaping the identities of trans‐synaptic signaling pathways. A series of recent studies provide evidence that diverse presynaptic cell adhesion proteins dictate the regulation of specific synaptic properties in postsynaptic neurons. Focusing on mammalian synaptic CAMs, this article outlines several exemplary cases supporting this notion and highlights how these trans‐synaptic signaling pathways collectively contribute to the specificity (...) and diversity of neural circuit architecture. (shrink)

How environmental mechanical forces affect cellular functions is a central problem in cell biology. Theoretical models of cellular biomechanics provide relevant tools for understanding how the contributions of deformable intracellular components and specific adhesion conditions at the cell interface are integrated for determining the overall balance of mechanical forces within the cell. We investigate here the spatial distributions of intracellular stresses when adherent cells are probed by magnetic twisting cytometry. The influence of the cell nucleus stiffness (...) on the simulated nonlinear torque-bead rotation response is analyzed by considering a finite element multi-component cell model in which the cell and its nucleus are considered as different hyperelastic materials. We additionally take into account the mechanical properties of the basal cell cortex, which can be affected by the interaction of the basal cell membrane with the extracellular substrate. In agreement with data obtained on epithelial cells, the simulated behaviour of the cell model relates the hyperelastic response observed at the entire cell scale to the distribution of stresses and strains within the nucleus and the cytoskeleton, up to cell adhesion areas. These results, which indicate how mechanical forces are transmitted at distant points through the cytoskeleton, are compared to recent data imaging the highly localized distribution of intracellular stresses. (shrink)

The reovirus cell attachment protein σ1 is a lollipopshaped structure with the fibrous tail anchored to the virion. Since it interacts with the cell receptor, σ1 is a major determinant of reovirus infectivity and tissue tropism. Studies on its structure‐function relationships have been facilitated by the fact that protein σ1 produced in any expression system is capable of binding to cell receptors. The use of site‐specific and deletion mutants has led to the identification and characterization of its (...) virion anchorage and receptor binding domains. Studies on the oligomeric status of σ1 have revealed that σ1 is a homotrimer and that two independent trimerization events at different loci (the N‐ and C‐terminal halves, respectively) of the protein, are involved in its generation. This also accounts for a clearly demonstrable dominant negative effect by a mutant subunit in a wild‐type/mutant σ1 heterotrimer. Current efforts are focused on the involvement of chaperones in the generation of σ1 and on events that take place upon σ1 binding to the cell receptor. Protein σ1 has therefore become an excellent model system for the study of both virus attachment and protein oligomerization and folding mechanisms. (shrink)

Asymmetric cell division generates cell diversity and contributes to cellular aging and rejuvenation. Here, we review the molecular mechanisms enabling budding yeast to recognize spindle pole bodies (SPB, centrosome equivalent) based on their age, and guide their non‐random mitotic segregation: SPB inheritance requires the distinction of old from new SPBs and is regulated by the SPB‐inheritance network (SPIN) and the mitotic exit network (MEN). The SPIN marks the pre‐existing SPB as old and the MEN recognizes these marks translating (...) them into spindle orientation. We next revisit other molecules and structures that partition depending on their age rather than their abundance at mitosis as, for example, DNA, centrosomes, mitochondria, and histones in yeast and other systems. The recurrence of this differential behavior suggests a functional significance for numerous cell types, which we then discuss. We conclude that non‐random segregation may facilitate asymmetric cell fate determination and thereby indirectly aging and rejuvenation. (shrink)

The view is presented that extracellular architecture in plant cell walls results from an interplay between molecular self‐assembly and mechanical reorientation due to growth forces. A key initial self‐assembly step may involve hemicelluloses. It is suggested that hemicelluloses may self‐assemble into a helicoid via a cholesteric liquid crystalline phase; the detailed molecular structure of hemicelluloses (stiff backbone, bulky side chains, and the presence of asymmetric carbon atoms) is shown to be consistent with cholesteric requirements for such self‐assembly. Since hemicelluloses (...) are hydrogen‐bonded to the periphery of cellulose microfibrils, the cellulose could then itself become helicoidally arranged. Such ‘universal plywood’ structure is found in the walls of a wide variety of plants, and in several types of cell (including wood). The permanent effects of growth stresses on patterns seen in sections of helicoids are displayed by computer graphics plots, and the expected changes in stiffness are calculated. (shrink)

The formation of DNA photoproducts by ultraviolet (UV) light is responsible for induction of mutations and development of skin cancer. To understand UV mutagenesis, it is important to know the mechanisms of formation and repair of these lesions. Cyclobutane pyrimidine dimers and (6–4)photoproducts are the two major classes of UV‐induced DNA lesions. Their distribution along DNA sequences in vivo is strongly influenced by nucleosomes and other DNA binding proteins. Repair of UV photoproducts is dependent on the transcriptional status of the (...) sequences to be repaired and on the chromatin environment. Sensitive techniques are now available to study repair of UV damage at the level of nucleotide resolution in mammalian cells. With the aid of in vitro systems, the entire nucleotide excision repair process has been reconstituted from purified protein components with naked DNA as a substrate. Future work will focus on the development of in vitro assays for transcription‐coupled repair and repair in chromatin. (shrink)

When we perceive the external world, our brain has to deal with the incompleteness and uncertainty associated with sensory inputs, memory and prior knowledge. In theoretical neuroscience probabilistic approaches have received a growing interest recently, as they account for the ability to reason with incomplete knowledge and to efficiently describe perceptive and behavioral tasks. How can the probability distributions that need to be estimated in these models be represented and processed in the brain, in particular at the single cell (...) level? We consider the basic function carried out by photoreceptor cells which consists in detecting the presence or absence of light. We give a system-level understanding of the process of phototransduction based on a bayesian formalism: we show that the process of phototransduction is equivalent to a temporal probabilistic inference in a Hidden Markov Model (HMM), for estimating the presence or absence of light. Thus, the biochemical mechanisms of phototransduction underlie the estimation of the current state probability distribution of the presence of light. A classical descriptive model describes the interactions between the different molecular messengers, ions, enzymes and channel proteins occurring within the photoreceptor by a set of nonlinear coupled differential equations. In contrast, the probabilistic HMM model is described by a discrete recurrence equation. It appears that the binary HMM has a general solution in the case of constant input. This allows a detailed analysis of the dynamics of the system. The biochemical system and the HMM behave similarly under steady-state conditions. Consequently a formal equivalence can be found between the biochemical system and the HMM. Numerical simulations further extend the results to the dynamic case and to noisy input. All in all, we have derived a probabilistic model equivalent to a classical descriptive model of phototransduction, which has the additional advantage of assigning a function to phototransduction. The example of phototransduction shows how simple biochemical interactions underlie simple probabilistic inferences. (shrink)

The YAP/TAZ family of transcriptional co‐activators drives cell proliferation in epithelial tissues and cancers. Yet, how YAP and TAZ are physiologically regulated remains unclear. Here we review recent reports that YAP and TAZ act primarily as sensors of epithelial cell polarity, being inhibited when cells differentiate an apical membrane domain, and being activated when cells contact the extracellular matrix via their basal membrane domain. Apical signalling occurs via the canonical Crumbs/CRB‐Hippo/MST‐Warts/LATS kinase cascade to phosphorylate and inhibit YAP/TAZ. Basal (...) signalling occurs via Integrins and Src family kinases to phosphorylate and activate YAP/TAZ. Thus, YAP/TAZ is localised to the nucleus in basal stem/progenitor cells and cytoplasm in differentiated squamous cells or columnar cells. In addition, other signals such as mechanical forces, tissue damage and possibly receptor tyrosine kinases (RTKs) can influence MST‐LATS or Src family kinase activity to modulate YAP/TAZ activity. (shrink)

Programmed cell death (PCD) is a process aimed at the removal of redundant, misplaced, or damaged cells and it is essential to the development and maintenance of multicellular organisms. In contrast to the relatively well‐described cell death pathway in animals, often referred to as apoptosis, mechanisms and regulation of plant PCD are still ill‐defined. Several morphological and biochemical similarities between apoptosis and plant PCD have been described, including DNA laddering, caspase‐like proteolytic activity, and cytochrome c release from mitochondria. (...) Reactive oxygen species (ROS) have emerged as important signals in the activation of plant PCD. In addition, several plant hormones may exert their respective effects on plant PCD through the regulation of ROS accumulation. The possible plant PCD regulators discussed in this review are integrated in a model that combines plant‐specific regulators with mechanisms functionally conserved between animals and plants. BioEssays 25:47–57, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

Imagine cells that live in a high‐gradient magnetic field (HGMF). Through what mechanisms do the cells sense a non‐uniform magnetic field and how such a field changes the cell fate? We show that magnetic forces generated by HGMFs can be comparable to intracellular forces and therefore may be capable of altering the functionality of an individual cell and tissues in unprecedented ways. We identify the cellular effectors of such fields and propose novel routes in cell biology predicting (...) new biological effects such as magnetic control of cell‐to‐cell communication and vesicle transport, magnetic control of intracellular ROS levels, magnetically induced differentiation of stem cells, magnetically assisted cell division, or prevention of cells from dividing. On the basis of experimental facts and theoretical modeling we reveal timescales of cellular responses to high‐gradient magnetic fields and suggest an explicit dependence of the cell response time on the magnitude of the magnetic field gradient. (shrink)

For decades, myxobacteria have been spotlighted as exemplars of social “wolf‐pack” predation, communally secreting antimicrobial substances into the shared public milieu. This behavior has been described as cooperative, becoming more efficient if performed by more cells. However, laboratory evidence for cooperativity is limited and of little relevance to predation in a natural setting. In contrast, there is accumulating evidence for predatory mechanisms promoting “selfish” behavior during predation, which together with conflicting definitions of cooperativity, casts doubt on whether microbial “wolf‐pack” predation (...) really is cooperative. Here, it is hypothesized that public‐goods‐mediated predation is not cooperative, and it is argued that a holistic model of microbial predation is needed, accounting for predator and prey relatedness, social phenotypes, spatial organization, activity/specificity/transport of secreted toxins, and prey resistance mechanisms. Filling such gaps in our knowledge is vital if the evolutionary benefits of potentially costly microbial behaviors mediated by public goods are to be properly understood. (shrink)

This paper examines a case of failed interdisciplinary collaboration, between experimental stem cell research and theoretical systems biology. Recently, two groups of theoretical biologists have proposed dynamical systems models as a basis for understanding stem cells and their distinctive capacities. Experimental stem cell biologists, whose work focuses on manipulation of concrete cells, tissues and organisms, have largely ignored these proposals. I argue that ‘failure to communicate’ in this case is rooted in divergent views of explanation: the theoretically-inclined modelers (...) are committed to a version of the covering-law view, while experimental stem cell biologists aim at mechanistic explanations. I propose a way to reconcile these two explanatory approaches to cell development, and discuss the significance of this result for interdisciplinary collaboration in systems biology and beyond. (shrink)

In 2006, Shinya Yamanaka and colleagues discovered how to reprogram terminally differentiated somatic cells to a pluripotent stem cell state. The resulting induced pluripotent stem cells (iPSCs) made a paradigm shift in the field, further nailing down the disproval of the long‐held dogma that differentiation is unidirectional. The prospect of using iPSCs for patient‐specific cell‐based therapies has been enticing. This promise, however, has been questioned in the last two years as several studies demonstrated intrinsic epigenetic and genomic anomalies (...) in these cells. Here, we not only review the recent critical studies addressing the genome integrity during the reprogramming process, but speculate about the underlying mechanisms that could create de novo genome damage in iPSCs. Finally, we discuss how much an elevated mutation load really matters considering the safety of future therapies with cells heavily cultured in vitro. (shrink)

The robustness of biological processes to perturbations has so far been mainly explored in unicellular organisms; multicellular organisms have been studied for developmental processes or in the special case of redundancy between gene duplicates. Here we explore the robustness of cell biological mechanisms of multicellular organisms in an evolutionary context. We propose that the reuse of similar cell biological mechanisms in different cell types of the same organism has evolutionary implications: (1) the maintenance of apparently redundant mechanisms (...) over evolutionary time may in part be explained by their differential requirement in various cell types; (2) the relative requirement for two alternative mechanisms may evolve among homologous cells in different organisms. We present examples of cell biological processes, such as centrosome separation in prophase, spindle formation or cleavage furrow positioning, that support the first proposition. We propose experimental tests of these hypotheses. (shrink)

Before a cell divides into two daughter cells, it typically doubles not only its DNA, but also its mass. Numerous studies in cells ranging from yeast to mammals have shown that cellular growth, stimulated by nutrients and/or growth factor signaling, is a prerequisite for cell cycle progression in most types of cells. The textbook view of growth‐regulated cell cycles is that growth signaling activates the transcription of G1 Cyclin genes to induce cell proliferation, and also stimulates (...) anabolic metabolism and cell growth in parallel. However, genetic knockout tests in model organisms indicate that this is not the whole story, and new studies show that additional, “smarter” mechanisms help to coordinate the cell cycle with growth itself. Here we summarize recent advances in this field, and discuss current models in which growth signaling regulates cell proliferation by targeting core cell cycle regulators via non‐transcriptional mechanisms. (shrink)

Much of the current research in regenerative medicine concentrates on stem-cell therapy that exploits the regenerative capacities of stem cells when injected into different types of human tissues. Although new therapeutic paths have been opened up by induced pluripotent cells and human mesenchymal cells, the rate of success is still low and mainly due to the difficulties of managing cell proliferation and differentiation, giving rise to non-controlled stem cell differentiation that ultimately leads to cancer. Despite being still (...) far from becoming a reality, these studies highlight the role of physical and biological constraints (e.g., cues and morphogenetic fields) placed by tissue microenvironment on stem cell fate. This asks for a clarification of the coupling of stem cells and microenvironmental factors in regenerative medicine. We argue that extracellular matrix and stem cells have a causal reciprocal and asymmetric relationship in that the 3D organization and composition of the extracellular matrix establish a spatial, temporal, and mechanical control over the fate of stem cells, which enable them to interact and control (as well as be controlled by) the cellular components and soluble factors of microenvironment. Such an account clarifies the notions of stemness and stem cell regeneration consistently with that of microenvironment. (shrink)

There are many morphologically distinct membrane structures with different functions at the surface of epithelial cells. Among these, adherens junctions (AJ) and tight junctions (TJ) are responsible for the mechanical linkage of epithelial cells and epithelial barrier function, respectively. In the process of new cell–cell adhesion formation between two epithelial cells, such as after wounding, AJ form first and then TJ form on the apical side of AJ. This process is very complicated because AJ formation triggers drastic changes (...) in the organization of actin cytoskeleton, the activity of Rho family of small GTPases, and the lipid composition of the plasma membrane, all of which are required for subsequent TJ formation. In this review, the authors focus on the relationship between AJ and TJ as a representative example of specialization of plasma membrane regions and introduce recent findings on how AJ formation promotes the subsequent formation of TJ. (shrink)

The appeal to mechanisms in scientific explanation is commonplace in contemporary philosophy of science. In short, mechanists argue that an explanation of a phenomenon consists of citing the mechanism that brings the phenomenon about. In this paper, we present an argument that challenges the universality of mechanistic explanation: in explanations of the contemporary features of the eukaryotic cell, biologists appeal to its symbiogenetic origin and therefore the notion of symbiogenesis plays the main explanatory role. We defend the notion that (...) symbiogenesis is non-mechanistic in nature and that any attempt to explain some of the contemporary features of the eukaryotic cell mechanistically turns out to be at least insufficient and sometimes fails to address the question that is asked. Finally, we suggest that symbiogenesis is better understood as a pragmatic scientific law and present an alternative non-mechanistic model of scientific explanation. In the model we present, the use of scientific laws is supposed to be a minimal requirement of all scientific explanations, since the purpose of a scientific explanation is to make phenomena expectable. Therefore, this model would help to understand biologists’ appeal to the notion of symbiosis and thus is shown to be better, for the case under examination, than the mechanistic alternative. (shrink)

Efforts from diverse disciplines, including evolutionary studies and biomechanical experiments, have yielded new insights into the genetic, signaling, and mechanical control of tooth formation and functions. Evidence from fossils and non‐model organisms has revealed that a common set of genes underlie tooth‐forming potential of epithelia, and changes in signaling environments subsequently result in specialized dentitions, maintenance of dental stem cells, and other phenotypic adaptations. In addition to chemical signaling, tissue forces generated through epithelial contraction, differential growth, and skeletal constraints act (...) in parallel to shape the tooth throughout development. Here recent advances in understanding dental development from these studies are reviewed and important gaps that can be filled through continued application of evolutionary and biomechanical approaches are discussed. (shrink)

Recent years have witnessed an explosion of the single-cell biochemical toolbox including chromosome conformation capture -based methods that provide novel insights into chromatin spatial organization in individual cells. The observations made with these techniques revealed that topologically associating domains emerge from cell population averages and do not exist as static structures in individual cells. Stochastic nature of the genome folding is likely to be biologically relevant and may reflect the ability of chromatin fibers to adopt a number of (...) alternative configurations, some of which could be transiently stabilized and serve regulatory purposes. Single-cell Hi-C approaches provide an opportunity to analyze chromatin folding in rare cell types such as stem cells, tumor progenitors, oocytes, and totipotent cells, contributing to a deeper understanding of basic mechanisms in development and disease. Here, we review key findings of single-cell Hi-C and discuss possible biological reasons and consequences of the inferred dynamic chromatin spatial organization. Single-cell Hi-C expands the molecular biology toolbox for studies of chromatin structure in individual cells. This technique allows one to analyze cell-to-cell variability in TAD and loop structure, and to capture chromosome conformation in rare cell types such as oocytes, totipotent cells, and tumor progenitors. (shrink)

Recent years have witnessed an explosion of the single-cell biochemical toolbox including chromosome conformation capture -based methods that provide novel insights into chromatin spatial organization in individual cells. The observations made with these techniques revealed that topologically associating domains emerge from cell population averages and do not exist as static structures in individual cells. Stochastic nature of the genome folding is likely to be biologically relevant and may reflect the ability of chromatin fibers to adopt a number of (...) alternative configurations, some of which could be transiently stabilized and serve regulatory purposes. Single-cell Hi-C approaches provide an opportunity to analyze chromatin folding in rare cell types such as stem cells, tumor progenitors, oocytes, and totipotent cells, contributing to a deeper understanding of basic mechanisms in development and disease. Here, we review key findings of single-cell Hi-C and discuss possible biological reasons and consequences of the inferred dynamic chromatin spatial organization. Single-cell Hi-C expands the molecular biology toolbox for studies of chromatin structure in individual cells. This technique allows one to analyze cell-to-cell variability in TAD and loop structure, and to capture chromosome conformation in rare cell types such as oocytes, totipotent cells, and tumor progenitors. (shrink)