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Abstract The structure and dynamics of the cell nucleus regulate nearly every facet of the cell. Changes in nuclear shape limit cell motility and gene expression. Although the nucleus is generally seen as the stiffest organelle in the cell, cells can nevertheless deform the nucleus to large strains by small mechanical stresses. Here, we show that the mechanical response of the cell nucleus exhibits active fluidization that is driven by the BRG 1 motor of the SWI/SNF/BAF chromatin-remodeling complex. Atomic force microscopy measurements show that the nucleus alters stiffness in response to the cell substrate stiffness, which is retained after the nucleus is isolated and that the work of nuclear compression is mostly dissipated rather than elastically stored. Inhibiting BRG 1 stiffens the nucleus and eliminates dissipation and nuclear remodeling both in isolated nuclei and in intact cells. These findings demonstrate a novel link between nuclear motor activity and global nuclear mechanics. 

Abstract Cellular mechanics encompass both mechanical properties that resist forces applied by the external environment and internally generated forces applied at the location of cell–cell and cell–matrix junctions. Here, the authors demonstrate that microindentation of cellular domes formed by cell monolayers that locally lift off the substrate provides insight into both aspects of cellular mechanics in multicellular structures. Using a modified Hertz contact equation, the force–displacement curves generated by a micro‐tensiometer are used to measure an effective dome stiffness. The results indicate the domes are consistent with the Laplace–Young relationship for elastic membranes, regardless of biochemical modulation of the RhoA‐ROCK signaling axis. In contrast, activating RhoA, and inhibiting ROCK both alter the relaxation dynamics of the domes deformed by the micro‐tensiometer, revealing an approach to interrogate the role of RhoA‐ROCK signaling in multicellular mechanics. A finite element model incorporating a Mooney–Rivlin hyperelastic constitutive equation to describe monolayer mechanics predicts effective stiffness values that are consistent with the micro‐tensiometer measurements, verifying previous measurements of the response of cell monolayers to tension. Overall, these studies establish microindentation of fluid‐filled domes as an avenue to investigate the contribution of cell‐generated forces to the mechanics of multicellular structures. 

Abstract Infection of human cells by pathogens, including SARS‐CoV‐2, typically proceeds by cell surface binding to a crucial receptor. The primary receptor for SARS‐CoV‐2 is the angiotensin‐converting enzyme 2 (ACE2), yet new studies reveal the importance of additional extracellular co‐receptors that mediate binding and host cell invasion by SARS‐CoV‐2. Vimentin is an intermediate filament protein that is increasingly recognized as being present on the extracellular surface of a subset of cell types, where it can bind to and facilitate pathogens’ cellular uptake. Biophysical and cell infection studies are done to determine whether vimentin might bind SARS‐CoV‐2 and facilitate its uptake. Dynamic light scattering shows that vimentin binds to pseudovirus coated with the SARS‐CoV‐2 spike protein, and antibodies against vimentin block in vitro SARS‐CoV‐2 pseudovirus infection of ACE2‐expressing cells. The results are consistent with a model in which extracellular vimentin acts as a co‐receptor for SARS‐CoV‐2 spike protein with a binding affinity less than that of the spike protein with ACE2. Extracellular vimentin may thus serve as a critical component of the SARS‐CoV‐2 spike protein‐ACE2 complex in mediating SARS‐CoV‐2 cell entry, and vimentin‐targeting agents may yield new therapeutic strategies for preventing and slowing SARS‐CoV‐2 infection.