Mechanobiology of organelles

   Our laboratory focuses on exploring the mechanisms by which mechanical signals are sensed and transmitted within cell organelles.

   Biochemical versus physical cues: Life is possible due to biochemical reactions that enable cells to organize and adapt to the environment. In addition to these reactions, physical and mechanical cues also play a role in cell organization and adaptation. For instance, gravity affects our physiology by impacting our cells, as seen in astronauts. We also know that mesenchymal stem cells can differentiate into neurons, myoblasts, or osteoblasts depending on the rigidity of the environment in which they are grown. Therefore, external physical parameters, in addition to biochemical reactions, have a significant impact on cell function. We are interested in understanding how mechanical and physical cues regulate cell physiology.

   In order to sense and respond to mechanical signals, cells contain mechanosensitive and mechanoresponsive molecules, some of which have been characterized by our group (Echarri, A. et al., Nature Communications, 2019; García-García et al., Nature Communications, 2022). Mechanosensitive molecules can be physically stretched, which modifies their conformation and function, for example by enhancing their binding to a substrate or creating new binding sites for another molecule. These changes are then converted into biochemical modifications, in a process known as mechanotransduction, which provides a molecular mechanism to interpret and adapt to external and internal mechanical cues. As a result, mechanotransduction pathways play a role in regulating a variety of physiological processes, including cell proliferation, differentiation, aging, inflammation, cell migration, and metabolism. Not surprisingly, mutations in genes associated with mechanotransduction pathways are often linked to human diseases, such as accelerated aging, muscular dystrophies, lipodystrophies, cardiac dysfunction, and cancer. Hence, it is crucial to understand the molecular mechanisms that govern the physiological and pathological adaptation of cells to mechanical signals.

   Multiple recent studies, including our own (Nature communications, 2022; Nature Communications, 2019; Curr Op Cell Biol, 2020; J Cell Science, 2015), have uncovered new mechanotransduction pathways, macromolecular complexes, complex cell structures, and even organelles that respond to mechanical signals. These findings, along with previous studies, strongly suggest that cells need to finely tune most, if not all, of their compartments, regions, and functional units in order to adapt to mechanical cues. Nevertheless, our understanding of the mechanosensitive and mechanotransduction pathways operating within cell organelles and other structures is still limited or even unknown in some cases. Our objective is to identify these pathways and contribute to the understanding of how mechanoresponsive pathways play a role in both physiological and pathological processes.