Shape shifters: How cells respond to 3D mechanical stiffness

Shape shifters: How cells respond to 3D mechanical stiffness

Time Stamp: February 19, 2024 1:41 AM
Source Node: 2487307
Feb 19, 2024 (Nanowerk News) Imagine a world inside your body where tiny cells are like workers building and repairing tissue structures. They interact with their surroundings, which include a scaffold called the extracellular matrix (ECM). This scaffold is like the construction site, where cells get instructions on what and how to do. Now, scientists have been exploring this construction site to understand how changing the stiffness of this scaffold, like making it softer or harder, affects a special type of cell called stem cells. These stem cells are like the all-purpose builders, capable of turning into different cell types to help with repairs. So, what’s so interesting about this? Well, imagine if we could influence how these cells behave by simply altering the stiffness of their construction site. How Cells Respond to 3D Mechanical Stiffness The team observed that the stiff hydrogels fostered nascent ECM production and remodeling, triggering a mechanotransduction cascade. These changes were driven by intracellular PI3AKT signaling, regulation of epigenetic modifiers, and activation of YAP/TAZ. (Image: Courtesy of the researchers) In a recent study published in the journal Biomaterials (“Stiffness assisted cell-matrix remodeling trigger 3D mechanotransduction regulatory programs”), Dr. Akhilesh Gaharwar, professor and director of research for the Department of Biomedical Engineering and Dr. Irtisha Singh, assistant professor in the Department of Cell Biology and Genetics have developed new class of hydrogels, a jelly-like materials to study how cell move and respond to stiffness. They utilized nanoparticles to make the scaffold stiffer, without changing anything else. It’s like adding more support beams to a building without changing the bricks. What they found was fascinating. “When the scaffold rigidity was increased, cells underwent morphological alterations and exhibited enhanced proliferative behavior, suggestive of accelerated growth signaling,” stated Gaharwar. “This phenomenon exemplifies ‘3D mechanotransduction’ – a process wherein cells sense and respond to the mechanical properties of their surrounding matrix.” But here’s where it gets even more exciting. When they introduced stem cells into this stiffer environment, something amazing happened. These stem cells also sensed the change in stiffness and transformed into specialized repair cells, ready to fix any damage. “3D mechanotransduction functions as an intricate cellular communication mechanism with the extracellular matrix,” explained Singh. “Alterations in matrix stiffness convey distinct signals, leading to divergent responses: in cancer cells, increased stiffness typically promotes aggressive phenotypes, whereas in stem cells, it can initiate differentiation into reparative lineages.” This discovery is incredibly important because it means we might be able to control how cells behave by manipulating the stiffness of their surroundings. In the context of cancer, it’s like we can send a signal to slow down the cancer cells and encourage the repair crew to come in and fix the damage. In simple terms, we’re learning how to speak the language of cells and give them instructions by changing the feel of their environment. This could open up new ways to understand and treat cancer, all by using the power of 3D mechanotransduction. While there’s still more to explore, this research offers hope for a future where we have better tools to fight this complex disease. Other collaborators include Dr. Tanmay Lele, a Cancer Prevention and Research Institute of Texas (CPRIT) scholar and a professor in the biomedical engineering department at Texas A&M University.

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