Why Microtubules run in Circles - Mechanical Hysteresis of the Tubulin Lattice

The fate of every eukaryotic cell subtly relies on the exceptional mechanical properties of microtubules. Despite significant efforts, understanding their unusual mechanics remains elusive. One persistent, unresolved mystery is the formation of long-lived arcs and rings, e.g. in kinesin-driven gliding assays. To elucidate their physical origin we develop a model of the inner workings of the microtubule's lattice, based on recent experimental evidence for a conformational switch of the tubulin dimer. We show that the microtubule lattice itself coexists in discrete polymorphic states. Curved states can be induced via a mechanical hysteresis involving torques and forces typical of few molecular motors acting in unison. This lattice switch renders microtubules not only virtually unbreakable under typical cellular forces, but moreover provides them with a tunable response integrating mechanical and chemical stimuli.Comment: 5 pages, 4 Movies in the Supplemen

Modeling crawling cell movement on soft engineered substrates

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.Self-propelled motion, emerging spontaneously or in response to external cues, is a hallmark of living organisms. Systems of self-propelled synthetic particles are also relevant for multiple applications, from targeted drug delivery to the design of self-healing materials. Self-propulsion relies on the force transfer to the surrounding. While self-propelled swimming in the bulk of liquids is fairly well characterized, many open questions remain in our understanding of self-propelled motion along substrates, such as in the case of crawling cells or related biomimetic objects. How is the force transfer organized and how does it interplay with the deformability of the moving object and the substrate? How do the spatially dependent traction distribution and adhesion dynamics give rise to complex cell behavior? How can we engineer a specific cell response on synthetic compliant substrates? Here we generalize our recently developed model for a crawling cell by incorporating locally resolved traction forces and substrate deformations. The model captures the generic structure of the traction force distribution and faithfully reproduces experimental observations, like the response of a cell on a gradient in substrate elasticity (durotaxis). It also exhibits complex modes of cell movement such as “bipedal” motion. Our work may guide experiments on cell traction force microscopy and substrate-based cell sorting and can be helpful for the design of biomimetic “crawlers” and active and reconfigurable self-healing materials.DFG, GRK 1558, Kollektive Dynamik im Nichtgleichgewicht: in kondensierter Materie und biologischen Systeme

The role of the nucleus for cell mechanics: an elastic phase field approach

The nucleus of eukaryotic cells typically makes up around 30 % of the cell volume and tends to be up to ten times stiffer than the surrounding cytoplasm. Therefore it is an important element for cell mechanics, but a quantitative understanding of its mechanical role is largely missing. Here we demonstrate that elastic phase fields can be used to describe dynamical cell processes in adhesive or confining environments in which the nucleus plays an important role. We first introduce and verify our computational method and then study several applications of large relevance. For cells on adhesive patterns, we find that nuclear stress is shielded by the adhesive pattern. For cell compression between two parallel plates, we obtain force-compression curves that allow us to extract an effective modulus for the cell-nucleus composite. For micropipette aspiration, the effect of the nucleus on the effective modulus is found to be much weaker, highlighting the complicated interplay between extracellular geometry and cell mechanics that is captured by our approach.Comment: 13 pages, 6 figure

Coarse-graining the vertex model and its response to shear

Tissue dynamics and collective cell motion are crucial biological processes. Their biological machinery is mostly known, and simulation models such as the "active vertex model" (AVM) exist and yield reasonable agreement with experimental observations like tissue fluidization or fingering. However, a good and well-founded continuum description for tissues remains to be developed. In this work we derive a macroscopic description for a two-dimensional cell monolayer by coarse-graining the vertex model through the Poisson bracket approach. We obtain equations for cell density, velocity and the cellular shape tensor. We then study the homogeneous steady states, their stability (which coincides with thermodynamic stability), and especially their behavior under an externally applied shear. Our results contribute to elucidate the interplay between flow and cellular shape. The obtained macroscopic equations present a good starting point for adding cell motion, morphogenetic and other biologically relevant processes.Comment: 14 pages, 11 figure