Short-term molecular polarization of cells on symmetric and asymmetric micropatterns

Abstract

The ability of cells to sense geometrical/physical constraints of the local environment is important for cell movements during development, immune surveillance, and in cancer invasion. In this paper, we quantify "front-rear'' polarization-the crucial step in initiating cell migration-based on the cytoskeleton and substrate adhesion anisotropy in micropatterned cells of well-defined shapes. We then show that the general viewpoint that asymmetric cell shape is one of the defining characteristics of polarized cells is incomplete. Specifically, we demonstrate that cells on circular micropatterned islands can exhibit asymmetric distribution of both filamentous actin (f-actin) and focal adhesions (FAs) as well as directional, lamellipodial-like ruffling activity. This asymmetry, however, is transient and persists only for the period of several hours during which actin filaments and adhesion structures reorganize into a symmetric peripheral arrangement. Cells on asymmetric tear-drop shape islands also display polarized f-actin and FAs, but the polarization axes are oriented towards the wide end of the islands. Polarization of actin filaments on tear-drop islands is short-term, while focal adhesions remain asymmetrically distributed for longer times. From a practical perspective, circular cells constitute a convenient experimental system, in which phenomena related to cell polarization are "decoupled'' from the effects of the cell's local curvature (constant along the circular cell's perimeter), while asymmetric (tear-drop) micropatterned cells standardize the organization of the motility machinery of polarized/moving cells. Both systems may prove useful for the design of diagnostic tools with which to probe and quantify ex vivo the motility/invasiveness status of cells from cancer patients.