Melissa Pappas
Christopher Madl, Assistant Professor in Materials Science and Engineering, has been awarded the prestigious Maximizing Investigators’ Research Award for Early Stage Investigators (MIRA) National Institutes of Health (NIH) grant to advance his pioneering research on the role of mechanical signals in cellular behavior. The $2 million grant will fund the next five years of Madl’s work in developing novel biomaterials platforms that mimic the mechanical properties of native tissues, offering new insights into how cells respond to the physical cues within their environments.
The project, titled Leveraging Protein-Engineered Biomaterials and Bioorthogonal Chemistries to Elucidate the Role of Non-Elastic Matrix Properties in Regulating Cell Fate, is set to significantly impact the fields of materials science, medicine and biology. Madl’s work has the potential to inform the development of cutting-edge therapeutic strategies for a wide array of diseases, including cancer, fibrosis and age-related disorders.
“This funding from the NIH provides the opportunity to develop new cell-interactive materials that capture the dynamic complexity of living systems,” says Madl. “This work will provide unprecedented insight into how cells sense their surroundings and how the changing cellular environment contributes to tissue dysfunction in disease and aging.”
Cell behavior is strongly influenced by the mechanical properties of the extracellular matrix (ECM), the dynamic polymeric network surrounding cells. These mechanical signals are essential for directing cellular processes such as adhesion, migration, division and differentiation. However, when the ECM is disrupted, as in diseases like cancer and fibrosis, it can lead to abnormal cellular behavior. While much research has focused on how the stiffness, or elasticity, of the ECM affects cells, there is still much to be understood about other mechanical cues, including force dissipation, plastic deformation and microstructure, and how they influence cellular processes.
“This grant will allow us to address these gaps by developing innovative biomaterials and engineered systems that allow for the independent and dynamic control of multiple mechanical parameters,” says Madl. “Our new platform will enable precise exploration of how different mechanical cues regulate cellular behavior and contribute to disease progression. We will also explore how mechanical changes in the ECM are involved in aging and age-related diseases, advancing our understanding of how these forces can either facilitate or hinder tissue regeneration.”
A major innovation in Madl’s project will be the use of bioorthogonal chemistries, molecules that don’t interact with the natural biology of an organism but that can track biological processes in action, and protein-engineered materials to enable on-demand manipulation of matrix stiffness, force dissipation and adhesion cues in 3D cell culture models. These advancements will provide new insights into how cells generate and respond to mechanical forces in environments that more closely resemble the natural conditions found in tissues. Additionally, the development of improved cellular force measurement techniques will deepen understanding of how these mechanical signals influence cellular behavior in both health and disease.
Madl’s research promises to pave the way for groundbreaking advances in regenerative medicine, cancer therapies and the treatment of age-related diseases, providing a foundation for new therapeutic strategies that can better restore tissue function and homeostasis.
Read more about Madl’s research here.