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.
Lolo FN, Walani N, Seemann E, Zalvidea D, Pavón DM, Cojoc G, Zamai M, Viaris de Lesegno C, Martínez de Benito F, Sánchez-Álvarez M, Uriarte JJ, Echarri A, Jiménez-Carretero D, Escolano JC, Sánchez SA, Caiolfa VR, Navajas D, Trepat X, Guck J, Lamaze C, Roca-Cusachs P, Kessels MM, Qualmann B, Arroyo M, Del Pozo MA. . Novel Caveolin1-dolines constitute a distinct and rapid mechanoadaptation system. Nature Cell Biology. 10.1038/s41556-022-01034-3.
Echarri, A . A Multisensory Network Drives Nuclear Mechanoadaptation. Biomolecules. doi: 10.3390/biom12030404.
García-García M, Sánchez-Perales S, Jarabo P, Calvo E, Huyton T, Fu L, Ng SC, Sotodosos-Alonso L, Vázquez J, Casas-Tintó S, Görlich D, Echarri A*, Del Pozo MA*. . Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP. Nature Communications. doi: 10.1038/s41467-022-28693-y.
Del Pozo MA, Lolo FN, Echarri A* . Caveolae: Mechanosensing and mechanotransduction devices linking membrane trafficking to mechanoadaptation. Current Opinion in Cell Biology. doi: 10.1016/j.ceb.2020.10.008.
Echarri A*, Pavón DM, Sánchez S, García-García M, Calvo E, Huerta-López C, Velázquez-Carreras D, Viaris de Lesegno C, Ariotti N, Lázaro-Carrillo A, Strippoli R, De Sancho D, Alegre-Cebollada J, Lamaze C, Parton RG, Del Pozo MA* . An Abl-FBP17 mechanosensing system couples local plasma membrane curvature and stress fiber remodeling during mechanoadaptation. Nature Communications. doi: 10.1038/s41467-019-13782-2.
Strippoli R, Echarri A, Del Pozo MA . Cell-Based Assays to Study ERK Pathway/Caveolin1 Interactions. Methods Molecular Biology. doi: 10.1007/978-1-4939-6424-6_12.
Echarri A*, Del Pozo MA* . Caveolae - mechanosensitive membrane invaginations linked to actin filaments. Journal of Cell Science. doi: 10.1242/jcs.153940.
Rey-Barroso J, Alvarez-Barrientos A, Rico-Leo E, Contador-Troca M, Carvajal-Gonzalez JM, Echarri A, Del Pozo MA, Fernandez-Salguero PM. . The Dioxin receptor modulates Caveolin-1 mobilization during directional migration: role of cholesterol. Cell Commun Signal, 12:57. doi: 10.1186/s12964-014-0057-7.
Echarri A y Del Pozo, MA. . Imaging the complexity, plasticity and dynamics of caveolae. Chapter in “Cell Membrane Nanodomains: from Biochemistry to Nanoscopy” CRC Press. Taylor & Francis Group LLC Editors. Pp 113-132
Currently applied to Proyecto Generación del Conocimiento. Proyect title: Identification and characterization of new mechanotransduction pathways in the mammalian nuclear envelope (MechNuc). Resolution expected in summer 2023.
I am recruiting students for TGF, TFM and FPU applicants. If you are interested in mechanobiology feel free to email me and visit our lab. You can find more information in our lab web page: