Determination of Contractile Forces Generated by Actin Fibre Networks

Abstract

Recent experimental studies entail the seeding of cells on an array of microneedles, with the formation of focal adhesions being restricted to the tips of the microneedles. Contractile stresses generated in the cell actin network are transmitted to the microneedle array via such discrete focal adhesions. In order to obtain an enhanced understanding of cytoskeletal contractility from such experiments novel computational models are developed. A constitutive material law to describe cytoskeletal contractile behaviour is formulated. Finite element simulations using experimentally observed cellular geometries and actin network connectivity allow for the determination of the relationship between sub-cellular stresses and microneedle displacements. Parameter studies are performed leading to an accurate calibration of the constitutive formulation based on experimentally measured microneedle deflections. Stresses and strains in the actin network are computed and the evolution of actin fibre properties and geometries is also uncovered. Another interesting phenomenon observed in the aforementioned experiments is the detaching of certain microneedles from the actin network under large contractile forces. Cohesive zone modelling is used to simulate such a debonding of discrete focal adhesions. Such modelling provides quantitative information concerning the strength of focal adhesion bonds. Simulation of the stress redistribution in the actin network and consequent changes in microneedle deflections yields valuable information regarding the contribution of individual actin fibres to cellular deformation.