@article {70049, title = {Vimentin intermediate filaments as structural and mechanical coordinators of mesenchymal cells.}, journal = {Nat Cell Biol}, year = {2025}, month = {2025 Aug 05}, abstract = {

Vimentin is a cytoskeletal intermediate filament protein that governs the form and function of mesenchymal cells, although the mechanistic details have been poorly understood. Here we highlight recent findings that reveal the diverse role of vimentin in dynamically organizing intracellular architecture and enhancing mechanical resilience. The exceptional deformability of vimentin can now be understood from its high-resolution three-dimensional structure resolved using cryo-electron microscopy. Vimentin also organizes the motion and positioning of numerous organelles, including mitochondria and the nucleus. Furthermore, it synergizes with the actin cytoskeleton to protect cells from extreme mechanical deformations. Finally, vimentin expression in epithelial-mesenchymal transitions has a functional role in tumour invasion analogous to embryonic development and wound healing. These recent developments emphasize the importance of understanding the multifaceted roles of vimentin intermediate filaments in human health and disease.

}, issn = {1476-4679}, doi = {10.1038/s41556-025-01713-x}, url = {https://doi.org/10.1038/s41556-025-01713-x}, author = {Guo, Ming and Wong, Ian Y and Moore, Andrew S and Medalia, Ohad and Lippincott-Schwartz, Jennifer and Weitz, David A and Goldman, Robert D} } @article {48858, title = {Cell volume change through water efflux impacts cell stiffness and stem cell fate.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, year = {2017}, month = {2017 Sep 25}, pages = {E8618-27}, abstract = {

Cells alter their mechanical properties in response to their local microenvironment; this plays a role in determining cell function and can even influence stem cell fate. Here, we identify a robust and unified relationship between cell stiffness and cell volume. As a cell spreads on a substrate, its volume decreases, while its stiffness concomitantly increases. We find that both cortical and cytoplasmic cell stiffness scale with volume for numerous perturbations, including varying substrate stiffness, cell spread area, and external osmotic pressure. The reduction of cell volume is a result of water efflux, which leads to a corresponding increase in intracellular molecular crowding. Furthermore, we find that changes in cell volume, and hence stiffness, alter stem-cell differentiation, regardless of the method by which these are induced. These observations reveal a surprising, previously unidentified relationship between cell stiffness and cell volume that strongly influences cell biology.

}, issn = {1091-6490}, doi = {10.1073/pnas.1705179114}, author = {Guo, Ming and Pegoraro, Adrian F and Mao, Angelo and Zhou, Enhua H and Arany, Praveen R and Han, Yulong and Burnette, Dylan T and Jensen, Mikkel H and Kasza, Karen E and Moore, Jeffrey R and Mackintosh, Frederick C and Fredberg, Jeffrey J and Mooney, David J and Lippincott-Schwartz, Jennifer and Weitz, David A} } @article {47625, title = {Probing the stochastic, motor-driven properties of the cytoplasm using force spectrum microscopy.}, journal = {Cell}, volume = {158}, year = {2014}, month = {2014 Aug 14}, pages = {822-32}, abstract = {

Molecular motors in cells typically produce highly directed motion; however, the aggregate, incoherent effect of all active processes also creates randomly fluctuating forces, which drive diffusive-like, nonthermal motion. Here, we introduce force-spectrum-microscopy (FSM) to directly quantify random forces within the cytoplasm of cells and thereby probe stochastic motor activity. This technique combines measurements of the random motion of probe particles with independent micromechanical measurements of the cytoplasm to quantify the spectrum of force fluctuations. Using FSM, we show that force\ fluctuations substantially enhance intracellular movement of small and large components. The fluctuations are three times larger in malignant cells than in their benign counterparts. We further demonstrate that vimentin acts globally to anchor organelles against randomly fluctuating forces in the cytoplasm, with no effect on their magnitude. Thus, FSM has broad applications for understanding the cytoplasm and its intracellular processes in relation to cell physiology in healthy and diseased states.

}, keywords = {Animals, Biomechanical Phenomena, Cytoplasm, Embryo, Mammalian, Fibroblasts, Mice, Microscopy, Atomic Force, Proteins, Vimentin}, issn = {1097-4172}, doi = {10.1016/j.cell.2014.06.051}, author = {Guo, Ming and Ehrlicher, Allen J and Jensen, Mikkel H and Renz, Malte and Moore, Jeffrey R and Goldman, Robert D and Lippincott-Schwartz, Jennifer and Mackintosh, Frederick C and Weitz, David A} }