LEAPS-MPS: Surface Morphological Effect on Biomolecular Attachment to Responsive Microgels for Tunable Biomimetic 3D-Cell Culture Scaffolds

Spelman College, Atlanta GA

Investigators

Abstract

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). Nontechnical Abstract: The extracellular matrix is a 3D-biocomposite network of proteins, minerals, and biomolecules that support the biochemical and structural requirements for cell function in surrounding tissues. An important challenge for biotechnologists has been to develop synthetic 3D-biocompsite scaffolds that mimic the native biomaterial properties of the extracellular matrix, so that malignant cell behaviors can be more effectively characterized, diagnosed, and properly treated. The future goal for this research is to develop biomimetic 3D-scaffolds from responsive biocompatible polymer microgel networks, which will better reflect the indigenous 3D physical chemical properties of the microenvironment that cells experience. The first step toward creating these platforms and the primary objective of this proposal is to understand the structure-function relationships that govern microgel surface functionality, one of the most important features for directing cell behavior in target tissues among the engineered 3D-biocompsite scaffold. This research will provide the necessary opportunity for Spelman College – small liberal arts undergraduate institution of Black women – to incorporate polymer materials chemistry into the chemistry & biochemistry curriculum, in the form of meritorious undergraduate research and classroom engagement. Importantly, it will be a prime opportunity for undergraduate students to learn a new and foundational branch of chemistry. Participation in this research will broaden participation in the STEM workforce and benefit society by training more professionals to address emerging societal problems. Technical Abstract: This proposal supports the future goal for the research program of creating tunable, multifunctional biomimetic 3D-cell culture scaffolds for determining the mechanisms that govern collective cell behavior in diseased tissues by understanding the interfacial parameters that govern biomolecular surface attachment between reactive functional groups on responsive microgels and target biomolecules. Responsive microgels are “smart” colloidal hydrogel particles that can adapt their size, morphology, and physical properties in response to an external stimulus (pH, temperature, ionic strength). Biomaterials mediate specific cellular responses and direct new tissue formation via biomolecular recognition, achieved by surface and bulk modification via chemical or physical methods with bioactive molecules. The central hypothesis is that chemical biomolecular attachment to responsive microgels is governed by microgel porosity and the accessibility of the reactive functional groups in the microgel, and that these factors can lead to profound changes in the mesostructure and morphology of future microgel-based biocomposites. This proposal describes the experimental approach for verifying the hypothesis, where biomolecular attachment concentration will be investigated according to the polymer segment density of structurally diverse microgel surfaces. The specific aims of the proposed work are to identify the role that 1) microgel porosity and 2) reactive functional group accessibility imparts on biomolecular attachment density and distribution. This research will provide new knowledge on the influence that surface structure has on biomolecular attachment, post surface functionalization chemistry. These findings will contribute towards the rational development of multifunctional hybrid biomaterials, including biomimetic 3D-cell culture scaffolds for tissue engineering and theranostic site-specific drug delivery. 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.