Physical biology最新文献

Velocity correlation is an important feature for animal groups performing collective motions. Previous studies have mostly focused on the velocity correlation in a single ecological context. It is unclear whether correlation characteristics vary in a single species in different contexts. Here, we studied the velocity correlations in jackdaw flocks in two different contexts: transit flocks where birds travel from one location to another, and mobbing flocks where birds respond to an external stimulus. We found that in both contexts, although the interaction rules are different, the velocity correlations remain scale-free, i.e. the correlation length (the distance over which the velocity of two individuals is similar) increases linearly with the group size. Furthermore, we found that the correlation length is independent of the group density for transit flocks, but increases with increasing group density in mobbing flocks. This result confirms a previous observation that birds obey topological interactions in transit flocks, but switch to metric interactions in mobbing flocks. Finally, in both contexts, the impact of group polarization on correlation length is not significant. Our results suggest that wild animals are always able to respond coherently to perturbations regardless of context.

This study investigates how the recent history of bacteria affects their attachment to a solid-liquid interface. We compare the attachment from a flowing suspension of the bacterium,Pseudomonas aeruginosaPAO1, after one of two histories: (a) passage through a tube packed with glass beads or (b) passage through an empty tube. The glass beads were designed to increase the rate of bacterial interactions with solid-liquid surfaces prior to observation in a flow cell. Analysis of time-lapse microscopy of the bacteria in the flow cells shows that the residence time distribution and surface density of bacteria differ for these two histories. In particular, bacteria exiting the bead-filled tube, in contrast to those bacteria exiting the empty tube, are less likely to attach to the subsequent flow cell window and begin surface growth. In contrast, when we compared two histories defined by different lengths of tubing, there was no difference in either the mean residence time or the surface density. In order to provide a framework for understanding these results, we present a phenomenological model in which the rate of bacterial surface density growth,dN(t)/dt, depends on two terms. One term models the initial attachment of bacteria to a surface, and is proportional to the nonprocessive cumulative residence time distribution for bacteria that attach and detach from the surface without cell division. The second term for the rate is proportional to the bacterial surface density and models surface cell division. The model is in surprisingly good agreement with the data even though the surface growth process is a complex interplay between attachment/detachment at the solid-liquid interface and cell division on the surface.

Nature has evolved a variety of mechanisms to build epithelial trees of diverse architectures within different organs and across species. Epithelial trees are elaborated through branch initiation and extension, and their morphogenesis ends with branch termination. Each of these steps of the branching process can be driven by the actions of epithelial cells themselves (epithelial-intrinsic mechanisms) or by the cells of their surrounding tissues (epithelial-extrinsic mechanisms). Here, we describe examples of how these mechanisms drive each stage of branching morphogenesis, drawing primarily from studies of the lung, kidney, salivary gland, mammary gland, and pancreas, all of which contain epithelial trees that form through collective cell behaviors. Much of our understanding of epithelial branching comes from experiments using mice, but we also include examples here from avian and reptilian models. Throughout, we highlight how distinct mechanisms are employed in different organs and species to build epithelial trees. We also highlight how similar morphogenetic motifs are used to carry out conserved developmental programs or repurposed to support novel ones. Understanding the unique strategies used by nature to build branched epithelia from across the tree of life can help to inspire creative solutions to problems in tissue engineering and regenerative medicine.

Cancer invasion and metastasis require remodeling of the adjacent extracellular matrix (ECM). In this mini review, we will cover the mechanisms of proteolytic degradation and the mechanical remodeling of the ECM by cancer cells, with a focus on invadopodia. Invadopodia are membrane protrusions unique to cancer cells, characterized by an actin core and by the focal degradation of ECM via matrix metalloproteases (MMPs). While ECM can also be remodeled, at lower levels, by focal adhesions, or internal collagen digestion, invadopodia are now recognized as the major mechanism for MMP-dependent pericellular ECM degradation by cancer cells. Recent evidence suggests that the completion of epithelial-mesenchymal transition may be dispensable for invadopodia and metastasis, and that invadopodia are required not only for mesenchymal, single cell invasion, but also for collective invasion. During collective invasion, invadopodia was then shown to be located in leader cells, allowing follower cells to move via cooperation. Collectively, this suggests that invadopodia function may be a requirement not only for later steps of metastasis, but also for early invasion of epithelial cells into the stromal tissue. Over the last decade, invadopodia studies have transitioned into in 3D andin vivosettings, leading to the confirmation of their essential role in metastasis in preclinical animal models. In summary, invadopodia may hold a great potential for individual risk assessment as a prognostic marker for metastasis, as well as a therapeutic target.

Tumor-associated collagen signature-3 (TACS-3) is a prognostic indicator for breast cancer survival. It is characterized by highly organized, parallel bundles of collagen fibers oriented perpendicular to the tumor boundary, serving as directional, confining channels for cancer cell invasion. Here we design a TACS-3-mimetic anisotropic, confined collagen I matrix and examine the relation between anisotropy of matrix, directed cellular migration, and anisotropy of cell membrane-the first direct contact between TACS-3 and cell-using Michigan Cancer Foundation-7 (MCF-7) cells as cancer-model. Using unidirectional freezing, we generated ∼50μm-wide channels filled with collagen I. Optical tweezer (OT) microrheology shows that anisotropic confinement increases collagen viscoelasticity by two orders of magnitude, and the elastic modulus is significantly greater along the direction of anisotropic confinement compared to that along the orthogonal direction, thus establishing matrix anisotropy. Furthermore, MCF-7 cells embedded in anisotropic collagen I, exhibit directionality in cellular morphology and migration. Finally, using customized OT to trap polystyrene probes bound to cell-membrane (and not to ECM) of either free cells or cells under anisotropic confinement, we quantified the effect of matrix anisotropy on membrane viscoelasticity, both in-plane and out-of-plane, vis-à-vis the membrane. Both bulk and viscous modulus of cell-membrane of MCF-7 cells exhibit significant anisotropy under anisotropic confinement. Moreover, the cell membrane of MCF-7 cells under anisotropic confinement is significantly softer (both in-plane and out-of-plane moduli) despite their local environment being five times stiffer than free cells. In order to test if the coupling between anisotropy of extracellular matrix and anisotropy of cell-membrane is regulated by cell-cytoskeleton, actin cytoskeleton was depolymerized for both free and confined cells. Results show that cell membrane viscoelasticity of confined MCF-7 cells is unaffected by actin de-polymerization, in contrast to free cells. Together, these findings suggest that anisotropy of ECM induces directed migration and correlates with anisotropy of cell-membrane viscoelasticity of the MCF-7 cells in an actin-independent manner.

Kinesin is a microtubule-associated motor protein which works in teams to carry the cellular cargo transport. Lipid rafts on membranous cargos reorganize, causing the motors present in these areas to physically cluster. Unregulated clustering of motors leads to diseases such as Leishmaniasis, Newmann-Pick disease, etc. Variousin-vitroand computational studies have reported improved cargo velocity and travel distance of a fluid cargo as compared to a rigid cargo. However, only cargo velocity increases with increase in membrane fluidity of a fluid cargo. Thermal and motor forces acting tangentially on a cargo generate random torque and motor torque respectively, leading to cargo rotation and motor tail sliding on cargo surface. However, it is unknown which of these forces/torques play a crucial role in improving the transport properties. Here, we use computational models that incorporate random torque, motor torque, and combination of both random and motor torques to understand how they influence the clustering of Kinesin motors on cargo surface due to drift and diffusion of their tails. These studies were performed at varying tail diffusivity to understand their effect on clustering of tails in dispersed and clustered arrangement. We find that in dispersed arrangement, random torque does not cause clustering, whereas motor torque is crucial for clustering of tails on cargo surface, and tails sliding due to both random and motor torques have fastest cargo transport and maximum cooperativity. In clustered arrangement, tails slide to form a broad and steady cluster whose size increases with tail diffusivity resulting in decreased cargo runlength, velocity and cooperativity. These findings suggest that increased tail diffusivity negatively impacts the cluster and cargo transport of tails in the clustered arrangement, whereas it aids physical clustering of tails and cargo transport in dispersed arrangement.

The retina hosts all processes needed to convert external visual stimuli into a neural code. Light phototransduction and its conversion into an electrical signal involve biochemical cascades, ionic regulations, and different kinds of coupling, among other relevant processes. These create a nonlinear processing scheme and light-dependent adaptive responses. The dynamical adaptation model formulated in recent years is an excellent phenomenological candidate to resume all these phenomena into a single feedforward processing scheme. In this work, we analyze this description in highly nonlinear conditions and find that responses do not match those resulting from a very detailed microscopic model, developed to reproduce electrophysiological recordings on horizontal cells. When a delayed light-dependent gain factor incorporates into the description, responses are in excellent agreement, even when spanning several orders of magnitude in light intensity, contrast, and duration, for simple and complex stimuli. This extended model may be instrumental for studies of the retinal function, enabling the linking of the microscopic domain to the understanding of signal processing properties, and further incorporated in spatially extended retinal networks.

Small gene effects involved in complex/omnigenic traits remain costly to analyse using current genome-wide association studies (GWAS) because of the number of individuals required to return meaningful association(s), a.k.a. study power. Inspired by field theory in physics, we provide a different method called genomic informational field theory (GIFT). In contrast to GWAS, GIFT assumes that the phenotype is measured precisely enough and/or the number of individuals in the population is too small to permit the creation of categories. To extract information, GIFT uses the information contained in the cumulative sums difference of gene microstates between two configurations: (i) when the individuals are taken at random without information on phenotype values, and (ii) when individuals are ranked as a function of their phenotypic value. The difference in the cumulative sum is then attributed to the emergence of phenotypic fields. We demonstrate that GIFT recovers GWAS, that is, Fisher's theory, when the phenotypic fields are linear (first order). However, unlike GWAS, GIFT demonstrates how the variance of microstate distribution density functions can also be involved in genotype-phenotype associations when the phenotypic fields are quadratic (second order). Using genotype-phenotype simulations based on Fisher's theory as a toy model, we illustrate the application of the method with a small sample size of 1000 individuals.