Matellan, C. | bioRxiv Science

bioRxiv2022

Retinoid acid receptor β mechanically regulates the activity of pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) is the most common and lethal form of pancreatic cancer, characterised by stromal remodelling, elevated matrix stiffness and high metastatic rate. Retinoids, compounds derived from vitamin A, have a history of clinical use in cancer for their anti-proliferative and differentiation effects, and more recently have been explored as anti-stromal therapies in PDAC for their ability to induce mechanical quiescence in cancer associated fibroblasts. Here we demonstrate that retinoic acid receptor {beta} (RAR-{beta}) transcriptionally represses myosin light chain 2 (MLC-2) expression, a key regulatory component of the contractile actomyosin machinery. In turn, MLC-2 downregulation results in decreased cytoskeletal stiffness and traction force generation, impaired response to mechanical stimuli via mechanosensing and reduced ability to invade through the basement membrane.

bioengineering↗

bioRxiv2022

Mesenchymal Stem Cells Sense the Toughness of Nanomaterials and Interfaces

Stem cells are known to sense and respond to a broad range of physical stimuli arising from their extra-cellular environment. In particular, the role of the mechanical properties (Youngs or shear modulus, viscoelasticity) of biomaterials has extensively been shown to have a significant impact on the adhesion, spreading, expansion and differentiation of stem cells. In turn, cells exert forces on their environment that can lead to striking changes in shape, size and contraction of associated tissues, and may result in mechanical disruption and functional failure. However, no study has so far correlated stem cell phenotype and biomaterials toughness. Indeed, disentangling toughness-mediated cell response from other mechanosensing processes has remained elusive as it is particularly challenging to uncouple Youngs or shear moduli from toughness, within a range relevant to cell-generated forces. In this report, we show how the design of macromolecular architecture of polymer nanosheets regulates interfacial toughness, independently to interfacial shear storage modulus, and how this, in turn, controls the expansion of mesenchymal stem cells at liquid interfaces.

bioengineering↗