Nature Materials volume 22, pages1409–1420 (2023).
The cell skeleton (cytoskeleton) is formed by multiple filaments of different mechanical properties, creating a dense mesh with diverse and complex responses. These cytoskeleton networks interact with the extracellular matrix (ECM) to determine the cell behavior. The paper by Kechagia et al. shows that laminin, a ubiquitous protein in ECM, interacts with the intracellular keratin network to mechanically shield the nucleus of breast cells, and increase its rigidity. These effects provide a mechanism to regulate the sensitivity of cells against external stimuli.
The conclusions of the paper are supported by a model set up by Pablo Sáez and Marino Arroyo, which allows quantifying the role of the actin network, the main component of the cytoskeleton, and myosin motors (other proteins that pull and create the actin flow within the cell) in conjunction with the keratin network. The model is based on a continuum description and considers the mechanical balance of actin and IFs, jointly with transport equations of acto-myosin and keratin network with advection-diffusion effects. The main assumptions of the mathematical model can be found in the Outreach Section in page 13 of the Newsletter 07.
Importantly, the model incorporates friction and viscosity of actin network, IFs and ECM. The set of coupled non-linear equations is solved by resorting to finite element techniques, which are later used to analyze different scenarios of control cells and mutants. The latter are used to understand important mechanical effects of laminin content in nuclear mechanotransduction.