Mitosis-Specific Mechanosensing and Contractile-Protein Redistribution Control Cell Shape

Abstract

Because cell-division failure is deleterious, promoting tumorigenesis in mammals, cells utilize numerous mechanisms to control their cell-cycle progression. Though cell division is considered a well-ordered sequence of biochemical events, cytokinesis, an inherently mechanical process, must also be mechanically controlled to ensure that two equivalent daughter cells are produced with high fidelity. Given that cells respond to their mechanical environment, we hypothesized that cells utilize mechanosensing and mechanical feedback to sense and correct shape asymmetries during cytokinesis. Because the mitotic spindle and myosin II are vital to cell division, we explored their roles in responding to shape perturbations during cell division. We demonstrate that the contractile proteins myosin II and cortexillin I redistribute in response to intrinsic and externally induced shape asymmetries. In early cytokinesis, mechanical load overrides spindle cues and slows cytokinesis progression while contractile proteins accumulate and correct shape asymmetries. In late cytokinesis, mechanical perturbation also directs contractile proteins but without apparently disrupting cytokinesis. Significantly, this response only occurs during anaphase through cytokinesis, does not require microtubules, and is independent of spindle orientation, but is dependent on myosin II. Our data provide evidence for a mechanosensory system that directs contractile proteins to regulate cell shape during mitosis.

Cell adhesion molecules regulate contractile ring-independent cytokinesis in Dictyostelium discoideum

“…To explain these, we proposed that Dictyostelium cells [5][6][7]: cytokinesis A, which is dependent on active contraction of a contractile ring and is independent of substrate adhesion, and cytokinesis B [4,5], or attachment-assisted mitotic cleavage [3], which does not depend on active contraction of a contractile ring but requires substrate adhesion. We have proposed that cytokinesis B is driven by oppositely oriented traction forces generated by two daughter cells, which separate the two cells by moving away from one another [5,6], although a similar but somewhat different hypothesis has also been proposed [32,33]. The aim of this study was to reveal the crosstalk among cell adhesion, cell migration and cytokinesis, cytokinesis B in particular, in Dictyostelium through examination of the functions of PAXB and VINA.…”

Cell shape regulation through mechanosensory feedback control

“…The major module responsible for cellular mechanosensing is the force-dependent accumulation of myosin II involving the assembly -disassembly of myosin II BTFs [10,12]. In our model, we coupled this to the viscoelastic properties of a cell to explain the biphasic mechanosensitive myosin accumulation and ensuing cellular deformation observed in WT and actin cross-linker-depleted mutant Dictyostelium cells.…”

“…For this reason, the signs in front of s ten ðr R Þ, Ds cross ðI cross Þ and Ds myo ðI myo Þ in the above equation are all negative. In practice, the accumulation of cross-linkers and myosin II differs, though there is a strong correlation between the two [10,14]. To keep the model simple, we assumed that the increase in accumulation of the cross-linkers is the same as that of myosin II; i.e.…”

“…When WT or genetically modified Dictyostelium cells are subjected to constant mechanical perturbation through a micropipette aspirator, myosin II is recruited to the site of deformation [10,[12][13][14] (figure 1a). The kinetics of myosin II accumulation in each of the cell types can be characterized as three distinct temporal phases: an initial accelerating accumulation, followed by a plateau, and subsequent decay (figure 2, left panels; [13,14]).…”

Mechanical impulses can control metaphase progression in a mammalian cell

“…In complex living tissues and organisms, cells have to adapt to compressive forces exerted by multiple surrounding cells. These mechanical interactions, which are intricately involved in cellular processes both mechanically and biochemically, thus have a strong impact on cellular functions (1)(2)(3)(4). Mechanical forces play an especially important role in chromosome segregation machinery, which is controlled by mechanochemical regulation (5)(6)(7).…”