Traction forces of cytokinesis measured with optically modified elastic substrata

Abstract

Animal cells dividing in culture undergo a dramatic sequence of morphological changes, characterized by cytoskeletal disassembly as cells round up, redistribution of actin, myosins and other cytoplasmic and surface molecules into the cleavage furrow, and respreading, before daughter cells finally separate at the mid-body. Knowledge of forces governing these movements is critical to understanding their mechanisms, including whether formation of the cleavage furrow results from increased force generation at the equator or relaxation at the poles, and whether traction force subsequently mediates cytofission of the intercellular bridge. We have quantitatively mapped traction forces in dividing cells, by extending the silicone-rubber substratum method to detect forces of nanonewtons to micronewtons. We used a new silicone polymer to fabricate substrata whose compliance can be adjusted precisely by ultraviolet irradiation. We show that traction force appears locally at the furrow in the absence of relaxation at the poles during cleavage. Force also rises as connected daughter cells respread and attempt to separate, suggesting that tension contributes to the severing of the intercellular bridge when cytokinesis is completed.

Novel Functions of Ect2 in Polar Lamellipodia Formation and Polarity Maintenance during “Contractile Ring-Independent” Cytokinesis in Adherent Cells

“…On highly adherent substrates, certain types of mammalian cells are also able to divide in an adhesion-dependent, contractile ring-independent manner when the activity of the contractile ring is blocked by the myosin II-specific inhibitor blebbistatin (Kanada et al, 2005). In addition, Burton and Taylor (1997) reported a case of successful division of a fibroblast that was driven by traction forces after regression of the initial equatorial furrow under physiological culture condi- tions. This observation can be interpreted to mean that cytokinesis B is activated when cells fail to properly complete cytokinesis A and that mammalian cytokinesis B serves as a backup mechanism.…”

Deregulation of HEF1 Impairs M-Phase Progression by Disrupting the RhoA Activation Cycle

“…We and others have also previously determined that overexpression of HEF1 impacts cell spreading, causing initial enhancement of spreading, and subsequent retraction van Seventer et al, 2001;Fashena et al, 2002). Defective cellular attachment can independently result in cytokinetic failure (Orly and Sato, 1979;Ben-Ze'ev and Raz, 1981), and it is well established in some models that force generation arising from spreading at the end of telophase assists in cytokinesis (Burton and Taylor, 1997;Gerald et al, 1998;Nagasaki et al, 2002). However, we have determined that plating HEF1-induced cells on fibronectin or laminin to enhance cell spreading had no appreciable effect on the frequency of defective cytokinesis or number of rounded cells with persistent post-mitotic bridges (our unpublished data).…”

Implications of a poroelastic cytoplasm for the dynamics of animal cell shape

“…We were drawn to consider poroelasticity by analysis of blebbing [12], a dramatic type of motility that many animal cells display when they divide [30,31] or undergo apoptosis [32]. Blebbing is typically a cyclic phenomenon where a bleb nucleates, expands, and contracts over 1-3 minutes without moving laterally ( figure 5 [33,34]).…”