CAREER: Harnessing Dynamic Cell-Scaffold Interactions to Develop Adaptive Biohybrid Systems

Non-Technical Summary

In the human body, we have cells in our muscle tissues that perpetually contract to allow us to move, breathe, and have a functional heart. For cardiac tissues, the contractile behavior of cardiomyocytes as their main cellular component serves as an important indicator whether these tissues are healthy or diseased. Here, the PI proposes to develop a class of materials that can be interfaced with cardiomyocytes and also have a capability to report real-time changes in cardiac contractility through read-outs based on changes in their optical properties.

Specifically, these materials will be made possible by using polymeric components that are force-sensitive or “mechanoresponsive” due to molecular-level rearrangements that they can afford in response to external mechanical stimuli such as cardiac contractions. These force-induced molecular bond transformations are proposed to lead to changes in the way that these soft materials absorb or emit light, therefore, serving as optical read-outs for biological force sensing.

These materials will also be designed to bear cell-adhering peptides that improve the sensing of contractile stress at the interface of cells and the proposed biomaterial. In addition to understanding how cellular contractions can cause molecular transformations that may lead to instantaneous changes in their optical properties, this project aims to use the proposed materials for assessing the long-term effects of contractile cells on the bulk properties of materials that serve as their scaffolds in vitro.

By developing a contractile cell-interfaceable biomaterial with force-sensing capability, the PI sets the stage for quantitatively visualizing biological forces in real-time and being able to directly assess how environmental parameters affect cardiac function through contractility. In the future, this class of adaptive materials could be adopted for model platforms used in screening drug cardiotoxicity and investigating mechanisms of debilitating cardiac diseases.

The proposed research will be integrated with educational objectives that aims to help with the recruitment, retention, and promotion of biomaterials researchers at multiple career stages, particularly those from historically underrepresented backgrounds. Technical Summary

Cell-generated forces play a crucial role in regulating several biological processes—from tissue morphogenesis to disease pathophysiology. Currently available measurement techniques enable multi-scale force quantification, but these often involve approaches that are destructive, focuses on 2D traction forces, and do not offer real-time measurements.

In this CAREER proposal, the PI proposes to develop a class of adaptive peptide biomaterials that exhibit reversible, quantifiable changes in optical properties in response to mechanobiological forces. This class of mechanochromic material will be engineered as hydrogel networks bearing force-responsive, π-conjugated chromophores and have covalent linkages that can autonomously rearrange in response to cardiac contractions.

The proposed adaptive biohybrid system can thus allow for in situ visualization of contractile forces that are directly correlated with cell/tissue health and function, and a platform to evaluate the dynamic mechanical interaction at biotic-abiotic interfaces. This sensory capability adds more functionality to conventional peptide bioscaffolds, and therefore, offers a transformative advance to bioscaffolds for tissue engineering applications that are only traditionally designed to recapitulate the composition, mechanical properties, and topography of native extracellular matrix (ECM) environments.

These efforts serve as a foundational pillar towards the PI’s long-term career goal, which is to leverage designer biomaterials that uniquely transduce optical or electronic phenomena at the cellular interface to control or probe biological processes at multiple spatiotemporal scales. Together with our proposed research activities on developing an adaptive biomaterial technology, we will implement educational activities such as summer workshops, mentorship activities, and public seminars that aims to strengthen the interdisciplinary training pipeline for the current and next generation of diverse biomaterials researchers.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.