Tissue viscoelasticity is the key to cellular response

Cells require biochemical and mechanical signals to function properly. Mechanobiology is the science that studies how cells recognize and respond to the mechanical properties of their environment. “One of the most important elements in the generation of mechanical signals is the extracellular matrix (ECM), a network of proteins that acts as a glue between cells, helping to form tissues,” explains Dr. Jorge Alegre-Cebollada, head of the molecular medicine group. Mechanics of the cardiovascular system at the Central Scientific Research Center.

OSB It influences cellular activity through mechanical properties such as stiffness and viscoelasticity, regulating cell migration, proliferation and differentiation. Changes in tissue stiffness are associated with diseases such as myocardial infarction and some types of cancer (pancreas and breast). However, it is not yet fully understood how cells simultaneously respond to stiffness and viscoelasticity, especially in harsh environments.

What the study published in the journal shows for the first time Achievements of science and under the direction of Dr. Alegre-Cebollada, it is how the ability of tissues to deform and regain their original shape (viscoelasticity) plays a fundamental role in the process by which a cell maintains a constant internal balance for proper functioning, a process called cellular homeostasis. .

“This work represents a new paradigm in our understanding of how cells respond to mechanical properties and may contribute to explanations, for example, of why some tumors are more aggressive than others, as well as better functioning of engineered tissues with biomedical applications.” emphasizes Dr. Alegre-Cebollada.

Through the development of new biomaterials and a computational model, the CNIC-led team figured out how cells respond to viscoelasticity.

Regulation of cellular response timing

According to the study, the viscoelasticity of the extracellular matrix, a property that has been little studied until now, plays a critical role in regulating the timing of the cellular response to a mechanical stimulus.

Thus, comments Dr. Carla Huerta-Lopez, the researcher who led the study, “just as a viscoelastic mattress takes time to regain its shape when we get up each morning, cells and tissues need time to recover from mechanical stimuli. , like a handshake or a blow.” That is, Huerta-Lopez explains, the time dependence of mechanical changes is controlled by viscoelasticity.”

In this work, the CNIC team developed protein-based biomaterials that mimic the mechanical behavior of the extracellular matrix.

Using such biomaterials, the authors identified the mechanism responsible for how viscoelasticity counteracts the stiffness response in unexpected ways.

According to the researchers, this model contradicts existing models and provides new explanations for how cells respond to the mechanical properties of the extracellular matrix.

The study was made possible thanks to funding received from the Ministry of Science, Innovation and Universities, the European Research Council (ERC) and the Community of Madrid through the interdisciplinary consortium Tec4Bio-CM. Notably, four principal investigators of Tec4Bio-CM were directly involved in the development of this work from CNIC, ICMM-CSIC and the Polytechnic University of Madrid.

Help Article:

Huerta-Lopez S, Clemente-Manteca A, Velasquez-Carreras D, Espinosa FM, Sanchez JG, Martinez-del-Pozo A, Garcia-Garcia M, Martin-Colomo S, Rodriguez-Blanco A, Esteban-Gonzalez R , Martin-Zamora F.M., Gutierrez-Rus L.I., Garcia R., Roca-Cusacs P., Elosegui-Artola A., Del Pozo M.A., Herrero-Galan E., Saez P., Plaza G.R., Alegre-Cebollada H. Cellular response to viscous extracellular matrix energy dissipation outweighs perception of high stiffness. Scientific Adv. 2024, November 15; 10(eadf9758). doi:10.1126/sciadv.adf9758

Fountain: CNIK