Impact of Dimensionality and Network Disruption on Microrheology of Cancer Cells in 3D Environments
Figure 6
Brownian dynamics simulations of active actin networks.
a) A 3D 3×3×3 µm3 (in the x, y, and z directions, respectively) domain with periodic boundary conditions on all sides, mimicking the cytoskeletal network in 3D. Actin filaments (blue) are polymerized from G-actin monomers and allowed to bind to myosin II motors (orange) and crosslinkers (yellow). Motors walk along two filaments toward their barbed ends, generating internal stress. b) A 3D 3×3×1 µm3 domain with periodic boundary conditions in the x and y directions and fixed boundaries in the z-direction, mimicking a 2D cell configuration. The actin network is more planarized, as the filaments align along the x-y plane. c,d,e) Average internal stresses in the x (blue), y (green), and z (red) directions for (c) a 3D network, (d) a 2D network with 1 µm height in the z-direction, and (e) a 2D network with 500nm height in the z-direction. 2D networks have larger stress fluctuations from the mean in the x and y directions (the plane of interest in experiments), but reduced fluctuations in z, as compared to 3D networks. 3D networks have comparable average internal stresses in all 3 dimensions. 2D networks have reduced average stresses in the z-direction (perpendicular to the plane of filament alignment), generating mechanical anisotropy. The stresses for each time point for each simulation were calculated by summing the tensional forces of filaments crossing a total area of 9 µm2 in each direction. Motors start walking and generating tension along filaments at time = 100 s.