Cytoskeletal Mechanics Regulating Amoeboid Cell Locomotion

Abstract

Migrating cells exert traction forces when moving. Amoeboid cell migration is a common type of cell migration that appears in many physiological and pathological processes and is performed by a wide variety of cell types. Understanding the coupling of the biochemistry and mechanics underlying the process of migration has the potential to guide the development of pharmacological treatment or genetic manipulations to treat a wide range of diseases. The measurement of the spatiotemporal evolution of the traction forces that produce the movement is an important aspect for the characterization of the locomotion mechanics. There are several methods to calculate the traction forces exerted by the cells. Currently the most commonly used ones are traction force microscopy methods based on the measurement of the deformation induced by the cells on elastic substrate on which they are moving. Amoeboid cells migrate by implementing a motility cycle based on the sequential repetition of four phases. In this paper we review the role that specific cytoskeletal components play in the regulation of the cell migration mechanics. We investigate the role of specific cytoskeletal components regarding the ability of the cells to perform the motility cycle effectively and the generation of traction forces. The actin nucleation in the leading edge of the cell, carried by the ARP2/3 complex activated through the SCAR/WAVE complex, has shown to be fundamental to the execution of the cyclic movement and to the generation of the traction forces. The protein PIR121, a member of the SCAR/WAVE complex, is essential to the proper regulation of the periodic movement and the protein SCAR, also included in the SCAR/WAVE complex, is necessary for the generation of the traction forces during migration. The protein Myosin II, an important F-actin cross-linker and motor protein, is essential to cytoskeletal contractility and to the generation and proper organization of the traction forces during migration.

Three-Dimensional Balance of Cortical Tension and Axial Contractility Enables Fast Amoeboid Migration

“…The molecular and structural origins of the traction forces are also unclear, as migrating cells lacking MyoII or F-actin crosslinkers are still able to exert significant traction forces (8)(9)(10)(11). Our biomechanical understanding of cell movement is complicated further because migrating cells exert significant normal forces (perpendicular to the substrate) in addition to the tangential ones (12)(13)(14)(15). The mechanism whereby the cells are able to generate these strong normal forces is not known, nor is the role of these normal forces in regulating the efficiency of motility.…”

Two-Layer Elastographic 3-D Traction Force Microscopy

“…2. These synthetic data mimic the substratum deformation generated by migrating amoeboid cells13, including the Physarum amoebae reported in the Results Section below (see also ref. 36).…”

“…Traction forces exerted by the cells are known to regulate not only cell locomotion but also many other cellular processes78. Several traction force microscopy methods have been developed to measure the forces exerted by stationary and/or migrating cells on flat elastic polymer-based hydrogels9101112131415. These gels exhibit a linearly elastic behavior in the range of the small deformations produced by the cells161718.…”

Measuring mechanical stress in living tissues

“…A major disadvantage is that retrieving the tractions from the displacements is an ill-posed problem and thus it is very sensitive to experimental noise. Furthermore, TFM 2D is by definition restricted to measuring tangential in-plane tractions, but deformations on flat gels might be due to out-of-plane tractions, resulting in errors in the traction field measured with TFM 2D 72,73 .…”