Seminars in cell & developmental biology最新文献

Plasmodiophora brassicae Wor., the clubroot pathogen, is the perfect example of an “atypical” plant pathogen. This soil-borne protist and obligate biotrophic parasite infects the roots of cruciferous crops, inducing galls or clubs that lead to wilting, loss of productivity, and plant death. Unlike many other agriculturally relevant pathosystems, research into the molecular mechanisms that underlie clubroot disease and Plasmodiophora-host interactions is limited. After release of the first P. brassicae genome sequence and subsequent availability of transcriptomic data, the clubroot research community have implicated the involvement of phytohormones during the clubroot pathogen’s manipulation of host development. Herein we review the main events leading to the formation of root galls and describe how modulation of select phytohormones may be key to modulating development of the plant host to the benefit of the pathogen. Effector-host interactions are at the base of different strategies employed by pathogens to hijack plant cellular processes. This is how we suspect the clubroot pathogen hijacks host plant metabolism and development to induce nutrient-sink roots galls, emphasizing a need to deepen our understanding of this master manipulator.

Pectobacterium and Dickeya species belonging to the Soft Rot Pectobacteriaceae (SRP) are one of the most devastating phytopathogens. They degrade plant tissues by producing an arsenal of plant cell wall degrading enzymes. However, SRP-plant interactions are not restricted to the production of these “brute force” weapons. Additionally, these bacteria apply stealth behavior related to (1) manipulation of the host plant via induction of susceptible responses and (2) formation of heterogeneous populations with functionally specialized cells. Our review aims to summarize current knowledge on SRP-induced plant susceptible responses and on the heterogeneity of SRP populations. The review shows that SRP are capable of adjusting the host's hormonal balance, inducing host-mediated plant cell wall modification, promoting iron assimilation by the host, stimulating the accumulation of reactive oxygen species and host cell death, and activating the synthesis of secondary metabolites that are ineffective in limiting disease progression. By this means, SRP facilitate host plant susceptibility. During host colonization, SRP populations produce various functionally specialized cells adapted for enhanced virulence, increased resistance, motility, vegetative growth, or colonization of the vascular system. This enables SRP to perform self-contradictory tasks, which benefits a population's overall fitness in various environments, including host plants. Such stealthy tactical actions facilitate plant-SRP interactions and disease progression.

Understanding the mechanism by which cells coordinate their differentiation and migration is critical to our understanding of many fundamental processes such as wound healing, disease progression, and developmental biology. Mathematical models have been an essential tool for testing and developing our understanding, such as models of cells as soft spherical particles, reaction-diffusion systems that couple cell movement to environmental factors, and multi-scale multi-physics simulations that combine bottom-up rule-based models with continuum laws. However, mathematical models can often be loosely related to data or have so many parameters that model behaviour is weakly constrained. Recent methods in machine learning introduce new means by which models can be derived and deployed. In this review, we discuss examples of mathematical models of aspects of developmental biology, such as cell migration, and how these models can be combined with these recent machine learning methods.

Epithelial cancer is the one of most lethal cancer type worldwide. Targeting the early stage of disease would allow dramatic improvements in the survival of cancer patients. The early stage of the disease is related to cancer cell spreading across surrounding healthy epithelium. Consequently, deeper insight into cell dynamics along the biointerface between epithelial and cancer (mesenchymal) cells is necessary in order to control the disease as soon as possible. Cell dynamics along this epithelial-cancer biointerface is the result of the interplay between various biological and physical mechanisms. Despite extensive research devoted to study cancer cell spreading across the epithelium, we still do not understand the physical mechanisms which influences the dynamics along the biointerface. These physical mechanisms are related to the interplay between physical parameters such as: (1) interfacial tension between cancer and epithelial subpopulations, (2) established interfacial tension gradients, (3) the bending rigidity of the biointerface and its impact on the interfacial tension, (4) surface tension of the subpopulations, (5) viscoelasticity caused by collective cell migration, and (6) cell residual stress accumulation. The main goal of this study is to review some of these physical parameters in the context of the epithelial/cancer biointerface elaborated on the model system such as the biointerface between breast epithelial MCF-10A cells and cancer MDA-MB-231 cells and then to incorporate these parameters into a new biophysical model that could describe the dynamics of the biointerface. We conclude by discussing three biophysical scenarios for cell dynamics along the biointerface, which can occur depending on the magnitude of the generated shear stress: a smooth biointerface, a slightly-perturbed biointerface and an intensively-perturbed biointerface in the context of the Kelvin-Helmholtz instability. These scenarios are related to the probability of cancer invasion.

Cancer invasion through the surrounding epithelium and extracellular matrix (ECM) is the one of the main characteristics of cancer progression. While significant effort has been made to predict cancer cells response under various drug therapies, much less attention has been paid to understand the physical interactions between cancer cells and their microenvironment, which are essential for cancer invasion. Considering these physical interactions on various co-cultured in vitro model systems by emphasizing the role of viscoelasticity, the tissue surface tension, solid stress, and their inter-relations is a prerequisite for establishing the main factors that influence cancer cell spread and develop an efficient strategy to suppress it. This review focuses on the role of viscoelasticity caused by collective cell migration (CCM) in the context of mono-cultured and co-cultured cancer systems, and on the modeling approaches aimed at reproducing and understanding these biological systems. In this context, we do not only review previously-published biophysics models for collective cell migration, but also propose new extensions of those models to include solid stress accumulated within the spheroid core region and cell residual stress accumulation caused by CCM.

The process by which biological systems such as cells, tissues and organisms acquire shape has been named as morphogenesis and it is central to a plethora of biological contexts including embryo development, wound healing, or even cancer. Morphogenesis relies in both self-organising properties of the system and in environmental inputs (biochemical and biophysical). The classical view of morphogenesis is based on the study of external biochemical molecules, such as morphogens. However, recent studies are establishing that the mechanical environment is also used by cells to communicate within tissues, suggesting that this mechanical crosstalk is essential to synchronise morphogenetic transitions and self-organisation. In this article we discuss how tissue interaction drive robust morphogenesis, starting from a classical biochemical view, to finalise with more recent advances on how the biophysical properties of a tissue feedback with their surroundings to allow form acquisition. We also comment on how in silico models aid to integrate and predict changes in cell and tissue behaviour. Finally, considering recent advances from the developmental biomechanics field showing that mechanical inputs work as cues that promote morphogenesis, we invite to revisit the concept of morphogen.

Scientific knowledge in the field of cell biology and mechanobiology heavily leans on cell-based in vitro experiments and models that favor the examination and comprehension of certain biological processes and occurrences across a variety of environments. Cell culture assays are an invaluable instrument for a vast spectrum of biomedical and biophysical investigations. The quality of experimental models in terms of simplicity, reproducibility, and combinability with other methods, and in particular the scale at which they depict cell fate in native tissues, is critical to advancing the knowledge of the comprehension of cell-cell and cell-matrix interactions in tissues and organs. Typically, in vitro models are centered on the experimental tinkering of mammalian cells, most often cultured as monolayers on planar, two-dimensional (2D) materials. Notwithstanding the significant advances and numerous findings that have been accomplished with flat biology models, their usefulness for generating further new biological understanding is constrained because the simple 2D setting does not reproduce the physiological response of cells in natural living tissues. In addition, the co-culture systems in a 2D stetting weakly mirror their natural environment of tissues and organs. Significant advances in 3D cell biology and matrix engineering have resulted in the creation and establishment of a new type of cell culture shapes that more accurately represents the in vivo microenvironment and allows cells and their interactions to be analyzed in a biomimetic approach. Contemporary biomedical and biophysical science has novel advances in technology that permit the design of more challenging and resilient in vitro models for tissue engineering, with a particular focus on scaffold- or hydrogel-based formats, organotypic cultures, and organs-on-chips, which cover the purposes of co-cultures. Even these complex systems must be kept as simplified as possible in order to grasp a particular section of physiology too very precisely. In particular, it is highly appreciated that they bridge the space between conventional animal research and human (patho)physiology. In this review, the recent progress in 3D biomimetic culturation is presented with a special focus on co-cultures, with an emphasis on the technological building blocks and endothelium-based co-culture models in cancer research that are available for the development of more physiologically relevant in vitro models of human tissues under normal and diseased conditions. Through applications and samples of various physiological and disease models, it is possible to identify the frontiers and future engagement issues that will have to be tackled to integrate synthetic biomimetic culture systems far more successfully into biomedical and biophysical investigations.

Animal tissues are composed of heterogenous cells, and their sorting into different compartments of the tissue is a pivotal process for organogenesis. Cells accomplish sorting by themselves—it is well known that singly dispersed cells can self-organize into tissue-like structures in vitro. Cell sorting is regulated by both biochemical and physical mechanisms. Adhesive proteins connect cells together, selecting particular partners through their specific binding properties, while physical forces, such as cell-cortical tension, control the cohesiveness between cells and in turn cell assembly patterns in mechanical ways. These processes cooperate in determining the overall cell sorting behavior. This article focuses on the ‘cadherin’ family of adhesion molecules as a biochemical component of cell-cell interactions, addressing how they regulate cell sorting by themselves or by cooperating with other factors. New ideas beyond the classical models of cell sorting are also discussed.