Small molecules are frontline therapeutics for many diseases; however, they are often limited by their poor solubility. Therefore, hydrophobic small molecules are often encapsulated or prepared as pure drug nanoparticles. Navitoclax, used to eliminate senescent cells, is one such small molecule that faces challenges in translation due to its hydrophobicity and toxic side effects.
View Article and Find Full Text PDFTissue-scale architecture and mechanical properties instruct cell behaviour under physiological and diseased conditions, but our understanding of the underlying mechanisms remains fragmentary. Here we show that extracellular matrix stiffness, spatial confinements and applied forces, including stretching of mouse skin, regulate mitochondrial dynamics. Actomyosin tension promotes the phosphorylation of mitochondrial elongation factor 1 (MIEF1), limiting the recruitment of dynamin-related protein 1 (DRP1) at mitochondria, as well as peri-mitochondrial F-actin formation and mitochondrial fission.
View Article and Find Full Text PDFCollective dynamics of cells in confined geometry regulate several biological processes including cell migration, proliferation, differentiation, and communication. In this work, combining simulation with experimental data, we studied the oscillatory motion of epithelial sheets in smaller areas of confinement, and we linked the monolayer maturation induced-jamming with the wave formation. We showed that epithelial cell populations with delayed jamming properties use the additional time available from this delay to coordinate their movement, generating wave motion in larger areas of confinement compared to control populations.
View Article and Find Full Text PDF