Matrix mechanics regulates epithelial defence against cancer by tuning dynamic localization of filamin

In epithelia, normal cells recognize and extrude out newly emerged transformed cells by competition. This process is the most fundamental epithelial defence against cancer, whose occasional failure promotes oncogenesis. However, little is known about what factors determine the success or failure of this defence. Here we report that mechanical stiffening of extracellular matrix attenuates the epithelial defence against HRasV12-transformed cells. Using photoconversion labelling, protein tracking, and loss-of-function mutations, we attribute this attenuation to stiffening-induced perinuclear sequestration of a cytoskeletal protein, filamin. On soft matrix mimicking healthy epithelium, filamin exists as a dynamically single population, which moves to the normal cell-transformed cell interface to initiate the extrusion of transformed cells. However, on stiff matrix mimicking fibrotic epithelium, filamin redistributes into two dynamically distinct populations, including a new perinuclear pool that cannot move to the cell-cell interface. A matrix stiffness-dependent differential between filamin-Cdc42 and filamin-perinuclear cytoskeleton interaction controls this distinctive filamin localization and hence, determines the success or failure of epithelial defence on soft versus stiff matrix. Together, our study reveals how pathological matrix stiffening leads to a failed epithelial defence at the initial stage of oncogenesis.

Caveolae promote successful abscission by controlling intercellular bridge tension during cytokinesis

During cytokinesis, the intercellular bridge (ICB) connecting the daughter cells experiences pulling forces, which delay abscission by preventing the assembly of the ESCRT scission machinery. Abscission is thus triggered by tension release, but how ICB tension is controlled is unknown. Here, we report that caveolae, which are known to control membrane tension upon mechanical stress in interphase cells, are located at the midbody, at the abscission site and at the ICB/cell interface in dividing cells. Functionally, the loss of caveolae delays ESCRT-III recruitment during cytokinesis and impairs abscission. This is the consequence of a 2-fold increase of ICB tension measured by laser ablation, associated with a local increase in myosin II activity at the ICB/cell interface. We thus propose that caveolae buffer membrane tension and limit contractibility at the ICB to promote ESCRT-III assembly and cytokinetic abscission. Altogether, this work reveals an unexpected connection between caveolae and the ESCRT machinery and the first role of caveolae in cell division.

Nanomedicine for the Diagnosis and Therapy of COVID-19

The coronavirus disease-2019 (COVID-19) pandemics caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading around the world due to its high infection rate, long incubation period, as well as lack of effective diagnosis and therapy or vaccines, which is tearing global health systems apart. It is an urgent demand for point-of-care diagnosis and effective treatment to prevent the spread of COVID-19. Currently, based on the rapid development of functional materials with unique physicochemical features through advanced fabrication and chemical modification, nanomaterials provide an emerging tool to detect SARS-CoV-2, inhibit the interplay in the virus and host cell interface, and enhance host immune response. In our manuscript, we summarized recent advances of nanomaterials for the diagnosis and therapy of COVID-19. The limitation, current challenges, and perspectives for the nano-diagnosis and nano-therapy of COVID-19 are proposed. The review is expected to enable researchers to understand the effect of nanomaterials for the diagnosis and therapy of COVID-19 and may catalyze breakthroughs in this area.