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The adaptive mechanical properties of soft and fibrous biological materials are relevant to their functionality. The emergence of the macroscopic response of these materials to external stress and intrinsic cell traction from local deformations of their structural components is not well understood. Here, we investigate the nonlinear elastic behavior of blood clots by combining microscopy, rheology, and an elastic network model that incorporates the stretching, bending, and buckling of constituent fibrin fibers. By inhibiting fibrin cross-linking in blood clots, we observe an anomalous softening regime in the macroscopic shear response as well as a reduction in platelet-induced clot contractility. Our model explains these observations from two independent macroscopic measurements in a unified manner, through a single mechanical parameter, the bending stiffness of individual fibers. Supported by experimental evidence, our mechanics-based model provides a framework for predicting and comprehending the nonlinear elastic behavior of blood clots and other active biopolymer networks in general.

 

Cells self-organize into functional, ordered structures during tissue morphogenesis, a process that is evocative of colloidal self-assembly into engineered soft materials. Understanding how intercellular mechanical interactions may drive the formation of ordered and functional multicellular structures is important in developmental biology and tissue engineering. Here, by combining an agent-based model for contractile cells on elastic substrates with endothelial cell culture experiments, we show that substrate deformation–mediated mechanical interactions between cells can cluster and align them into branched networks. Motivated by the structure and function of vasculogenic networks, we predict how measures of network connectivity like percolation probability and fractal dimension as well as local morphological features including junctions, branches, and rings depend on cell contractility and density and on substrate elastic properties including stiffness and compressibility. We predict and confirm with experiments that cell network formation is substrate stiffness dependent, being optimal at intermediate stiffness. We also show the agreement between experimental data and predicted cell cluster types by mapping a combined phase diagram in cell density substrate stiffness. Overall, we show that long-range, mechanical interactions provide an optimal and general strategy for multicellular self-organization, leading to more robust and efficient realizations of space-spanning networks than through just local intercellular interactions.

 

Force dipoles embedded in elastic fiber networks that represent for example, myosin motors in the cell cytoskeleton, can interact through their mechanical deformations of the network.

 

Many types of animal cells exert active, contractile forces and mechanically deform their elastic substrate, to accomplish biological functions such as migration. These substrate deformations provide a mechanism in principle by which cells may sense other cells, leading to long-range mechanical inter–cell interactions and possible self-organization. Here, inspired by cell mechanobiology, we propose an active matter model comprising self-propelling particles that interact at a distance through their mutual deformations of an elastic substrate. By combining a minimal model for the motility of individual particles with a linear elastic model that accounts for substrate-mediated, inter–particle interactions, we examine emergent collective states that result from the interplay of motility and long-range elastic dipolar interactions. In particular, we show that particles self-assemble into flexible, motile chains which can cluster to form diverse larger-scale compact structures with polar order. By computing key structural and dynamical metrics, we distinguish between the collective states at weak and strong elastic interaction strength, as well as at low and high motility. We also show how these states are affected by confinement within a channel geometry–an important characteristic of the complex mechanical micro-environment inhabited by cells. Our model predictions may be generally applicable to active matter with dipolar interactions ranging from biological cells to synthetic colloids endowed with electric or magnetic dipole moments. 

Morphogenetic dynamics of tissue sheets require coordinated cell shape changes regulated by global patterning of mechanical forces. Inspired by such biological phenomena, we propose a minimal mechanochemical model based on the notion that cell shape changes are induced by diffusible biomolecules that influence tissue contractility in a concentration-dependent manner – and whose concentration is in turn affected by the macroscopic tissue shape. We perform computational simulations of thin shell elastic dynamics to reveal propagating chemical and three-dimensional deformation patterns arising due to a sequence of buckling instabilities. Depending on the concentration threshold that actuates cell shape change, we find qualitatively different patterns. The mechanochemically coupled patterning dynamics are distinct from those driven by purely mechanical or purely chemical factors, and emerge even without diffusion. Using numerical simulations and theoretical arguments, we analyze the elastic instabilities that result from our model and provide simple scaling laws to identify wrinkling morphologies. 

The mechanical micro-environment of cells and tissues influences key aspects of cell structure and function, including cell motility. For proper tissue development, cells need to migrate, interact, and form contacts. Cells are known to exert contractile forces on underlying soft substrates and sense deformations in them. Here, we propose and analyze a minimal biophysical model for cell migration and long-range cell–cell interactions through mutual mechanical deformations of the substrate. We compute key metrics of cell motile behavior, such as the number of cell-cell contacts over a given time, the dispersion of cell trajectories, and the probability of permanent cell contact, and analyze how these depend on a cell motility parameter and substrate stiffness. Our results elucidate how cells may sense each other mechanically and generate coordinated movements and provide an extensible framework to further address both mechanical and short-range biophysical interactions. 

Dynamic lane formation and long-range active nematic alignment are reported using a geometry in which kinesin motors are directly coupled to a lipid bilayer, allowing for in-plane motor diffusion during microtubule gliding. We use fluorescence microscopy to image protein distributions in and below the dense two-dimensional microtubule layer, revealing evidence of diffusion-enabled kinesin restructuring within the fluid membrane substrate as microtubules collectively glide above. We find that the lipid membrane acts to promote filament–filament alignment within the gliding layer, enhancing the formation of a globally aligned active nematic state. We also report the emergence of an intermediate, locally ordered state in which apolar dynamic lanes of nematically aligned microtubules migrate across the substrate. To understand this emergent behavior, we implement a continuum model obtained from coarse graining a collection of self-propelled rods, with propulsion set by the local motor kinetics. Tuning the microtubule and kinesin concentrations as well as active propulsion in these simulations reveals that increasing motor activity promotes dynamic nematic lane formation. Simulations and experiments show that, following fluid bilayer substrate mediated spatial motor restructuring, the total motor concentration becomes enriched below the microtubule lanes that they drive, with the feedback leading to more dynamic lanes. Our results have implications for membrane-coupled active nematics in vivo as well as for engineering dynamic and reconfigurable materials where the structural elements and power sources can dynamically colocalize, enabling efficient mechanical work. 

Macromolecules can phase separate to form liquid condensates, which are emerging as critical compartments in fields as diverse as intracellular organization and soft materials design. A myriad of macromolecules, including the protein FUS, form condensates which behave as isotropic liquids. Here, we investigate the influence of filament dopants on the material properties of protein liquids. We find that the short, biopolymer filaments of actin spontaneously partition into FUS droplets to form composite liquid droplets. As the concentration of the filament dopants increases, the coalescence time decreases, indicating that the dopants control viscosity relative to surface tension. The droplet shape is tunable and ranges from spherical to tactoid as the filament length or concentration is increased. We find that the tactoids are well described by a model of a quasi bipolar liquid crystal droplet, where nematic order from the anisotropic actin filaments competes with isotropic interfacial energy from the FUS, controlling droplet shape in a size-dependent manner. Our results demonstrate a versatile approach to construct tunable, anisotropic macromolecular liquids.