FtsZ rings and helices: physical mechanisms for the dynamic alignment of biopolymers in rod-shaped bacteria.

In many bacterial species, the protein FtsZ forms a cytoskeletal ring that marks the future division site and scaffolds the division machinery. In rod-shaped bacteria, most frequently membrane-attached FtsZ rings or ring fragments are reported and occasionally helices. By contrast, axial FtsZ clusters have never been reported. In this paper, we investigate theoretically how dynamic FtsZ aggregates align in rod-shaped bacteria. We study systematically different physical mechanisms that affect the alignment of FtsZ polymers using a computational model that relies on autocatalytic aggregation of FtsZ filaments at the membrane. Our study identifies a general tool kit of physical and geometrical mechanisms by which rod-shaped cells align biopolymer aggregates. Our analysis compares the relative impact of each mechanism on the circumferential alignment of FtsZ as observed in rod-shaped bacteria. We determine spontaneous curvature of FtsZ polymers and axial confinement of FtsZ on the membrane as the strongest factors. Including Min oscillations in our model, we find that these stabilize axial and helical clusters on short time scales, but promote the formation of an FtsZ ring at the cell middle at longer times. This effect could provide an explanation to the long standing puzzle of transiently observed oscillating FtsZ helices in Escherichia coli cells prior to cell division.

3D Microenvironment Stiffness Regulates Tumor Spheroid Growth and Mechanics via p21 and ROCK.

The mechanical properties of cancer cells and their microenvironment contribute to breast cancer progression. While mechanosensing has been extensively studied using 2D substrates, much less is known about it in a physiologically more relevant 3D context. Here it is demonstrated that breast cancer tumor spheroids, growing in 3D polyethylene glycol-heparin hydrogels, are sensitive to their environment stiffness. During tumor spheroid growth, compressive stresses of up to 2 kPa build up, as quantitated using elastic polymer beads as stress sensors. Atomic force microscopy reveals that tumor spheroid stiffness increases with hydrogel stiffness. Also, constituent cell stiffness increases in a Rho associated kinase (ROCK)- and F-actin-dependent manner. Increased hydrogel stiffness correlated with attenuated tumor spheroid growth, a higher proportion of cells in G0/G1 phase, and elevated levels of the cyclin-dependent kinase inhibitor p21. Drug-mediated ROCK inhibition not only reverses cell stiffening upon culture in stiff hydrogels but also increases tumor spheroid growth. Taken together, a mechanism by which the growth of a tumor spheroid can be regulated via cytoskeleton rearrangements in response to its mechanoenvironment is revealed here. Thus, the findings contribute to a better understanding of how cancer cells react to compressive stress when growing under confinement in stiff environments.