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Register a new userCytoskeletal Anisotropy Controls Geometry and Forces of Adherent Cells
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We investigate the geometrical and mechanical properties of adherent cells characterized by a highly anisotropic actin cytoskeleton. Using a combination of theoretical work and experiments on micropillar arrays, we demonstrate that the shape of the cell edge is accurately described by elliptical arcs, whose eccentricity expresses the degree of anisotropy of the internal cell stresses. This results in a spatially varying tension along the cell edge, that significantly affects the traction forces exerted by the cell on the substrate. Our work highlights the strong interplay between cell mechanics and geometry and paves the way towards the reconstruction of cellular forces from geometrical data.
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Gaining access to the cell interior is fundamental for many applications, such as electrical recording, drug and biomolecular delivery. A very promising technique consists of culturing cells on nano/micro pillars. The tight adhesion and high local deformation of cells in contact with nanostructures can promote the permeabilization of lipids at the plasma membrane, providing access to the internal compartment. However, there is still much experimental controversy regarding when and how the intracellular environment is targeted and the role of the geometry and interactions with surfaces. Consequently, we investigated, by coarse-grained molecular dynamics simulations of the cell membrane, the mechanical properties of the lipid bilayer under high strain and bending conditions. We found out that a high curvature of the lipid bilayer dramatically lowers the traction force necessary to achieve membrane rupture. Afterwards, we experimentally studied the permeabilization rate of cell membrane by pillars with comparable aspect ratios but different sharpness values at the edges. The experimental data support the simulation results: even pillars with diameters in the micron range may cause local membrane disruption when their edges are sufficiently sharp. Therefore, the permeabilization likelihood is connected to the local geometric features of the pillars rather than diameter or aspect ratio. The present study can also provide significant contributions to the design of 3D biointerfaces for tissue engineering and cellular growth.
Cytoskeletal motor proteins are involved in major intracellular transport processes which are vital for maintaining appropriate cellular function. The motor exhibits distinct states of motility: active motion along filaments, and effectively stationary phase in which it detaches from the filaments and performs passive diffusion in the vicinity of the detachment point due to cytoplasmic crowding. The transition rates between motion and pause phases are asymmetric in general, and considerably affected by changes in environmental conditions which influences the efficiency of cargo delivery to specific targets. By considering the motion of molecular motor on a single filament as well as a dynamic filamentous network, we present an analytical model for the dynamics of self-propelled particles which undergo frequent pause phases. The interplay between motor processivity, structural properties of filamentous network, and transition rates between the two states of motility drastically changes the dynamics: multiple transitions between different types of anomalous diffusive dynamics occur and the crossover time to the asymptotic diffusive or ballistic motion varies by several orders of magnitude. We map out the phase diagrams in the space of transition rates, and address the role of initial conditions of motion on the resulting dynamics.
Metabolic oscillations in single cells underlie the mechanisms behind cell synchronization and cell-cell communication. For example, glycolytic oscillations mediated by biochemical communication between cells may synchronize the pulsatile insulin secretion by pancreatic tissue, and a link between glycolytic synchronization anomalies and type-2 diabetes has been hypotesized. Cultures of yeast cells have provided an ideal model system to study synchronization and propagation waves of glycolytic oscillations in large populations. However, the mechanism by which synchronization occurs at individual cell-cell level and overcome local chemical concentrations and heterogenic biological clocks, is still an open question because of experimental limitations in sensitive and specific handling of single cells. Here, we show how the coupling of intercellular diffusion with the phase regulation of individual oscillating cells induce glycolytic synchronization waves. We directly measure the single-cell metabolic responses from yeast cells in a microfluidic environment and characterize a discretized cell-cell communication using graph theory. We corroborate our findings with simulations based on a kinetic detailed model for individual yeast cells. These findings can provide insight into the roles cellular synchronization play in biomedical applications, such as insulin secretion regulation at the cellular level.
We develop a general theory for active viscoelastic materials made of polar filaments. This theory is motivated by the dynamics of the cytoskeleton. The continuous consumption of a fuel generates a non equilibrium state characterized by the generation of flows and stresses. Our theory can be applied to experiments in which cytoskeletal patterns are set in motion by active processes such as those which are at work in cells.
The deep connection between thermodynamics, computation, and information is now well established both theoretically and experimentally. Here, we extend these ideas to show that thermodynamics also places fundamental constraints on statistical estimation and learning. To do so, we investigate the constraints placed by (nonequilibrium) thermodynamics on the ability of biochemical signaling networks within cells to estimate the concentration of an external signal. We show that accuracy is limited by energy consumption, suggesting that there are fundamental thermodynamic constraints on statistical inference.
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