CAREER: Biologically Inspired Platforms: Finding The Tricks Worth Mimicking In The Extracellular Matrix

Cornell University, Ithaca NY

Investigators

Abstract

Non-Technical Section This CAREER Award supported by the Biomaterials program in the Division of Materials Research seeks to study the structural and mechanical properties of the extracellular matrix (ECM). The extracellular matrix (ECM) is a multi-protein network used by cells to communicate with their environment. The research objectives of this Faculty Early Career Development (CAREER) project are (i) to characterize both structure and mechanics of the ECM from the protein (nanoscopic) to the cell (microscopic) level, and (ii) to exploit such fundamental understanding to engineer cell culture platforms for investigating vascularization mechanisms in functional and pathological (cancer) environments. Given the extensive interdisciplinary nature of this research, the primary educational goals of this program are to introduce students (K-12, undergraduate, and graduate) and teachers (GK-12 program) to the fields of (and the tools used in) materials and biomaterials science, biomechanics, protein physics, and cell biology. The PI will also train undergraduate and graduate students for future jobs in biomaterials science and/or engineering through (i) mentoring students from freshman to graduate level in research and (ii) integrating research into her three undergraduate and graduate level interdisciplinary courses taught across seven departments at Cornell. Technical Section Living cells sense and respond to their microenvironment through chemical and physical interactions determined by the adjacent cells and by the surrounding extracellular matrix (ECM) fibrillar network. The main goal of this Faculty Early Career Development (CAREER) project is to study both structural and mechanical properties of the two major building blocks of ECM structures (fibronectin and collagen) from the fiber to the cellular/tissue level. The strength of this program lies in the interdisciplinary approach that combines the PI's demonstrated expertise in (i) FRET (Fluorescence Resonance Energy Transfer) conformational mapping, and (ii) mechanical characterization of biomaterials at the nano-, and the microscopic scales. By combining these efforts, the PI will generate a fundamental understanding of the regulatory mechanisms governing ECM composition, conformation and mechanics, which will then enable the design of 2D and 3D cell culture platforms with controlled mechanobiological properties for investigating vascularization mechanisms in physiological and pathological (cancer) environments. This project has implications not only in biomaterials science but also in regenerative medicine and tissue engineering due to the fundamental role of the ECM in development and diseases such as cancer; it will also be of importance in its capacity not only to promote new approaches in cell-matrix interactions research, but also to expose K-12, undergraduate, and graduate students to a wide range of technological innovations.