AVS 62nd International Symposium & Exhibition
    Biomaterial Interfaces Wednesday Sessions
       Session BI-WeM

Paper BI-WeM5
Molecular Modeling of Biofunctionalized Hydrogels to Guide Hydrogel Design

Wednesday, October 21, 2015, 9:20 am, Room 211D

Session: Biomolecules at Interfaces
Presenter: Robert Latour, Clemson University
Authors: X. Li, Clemson University
M.L. Becker, University of Akron
N.S. Murthy, Rutgers University
R.A. Latour, Clemson University
Correspondent: Click to Email
Peptide-functionalized PEG-based hydrogels represent the workhorse material for tissue engineering and regenerative medicine applications because of their potential to mimic the extracellular matrix and serve as a substrate to direct cellular response. In order for a bioconjugated hydrogel to exhibit its intended bioactivity, the peptides that are tethered within the hydrogel must be accessible at the hydrogel surface for cell-receptor binding. Surface availability for a given peptide and hydrogel system will be a function of design parameters such as tether length, tether structure, and hydrogel crosslinking density. While the surface-accessibility of the peptide can be readily assessed experimentally, reasons for low accessibility (if encountered) are not easily determined. To address this type of problem, we are developing molecular modeling and simulation methods that will provide the ability to understand and visualize hydrogel behavior at an atomistic level to serve as a potentially powerful tool for hydrogel design. We are developing the molecular models using a multiscale approach. Coarse-grained (CG) parameters are first obtained from all-atom models of the various structural elements of the hydrogel system in aqueous solution using the polymer consistent force field (PCFF). A coarse-grained structure of the hydrogel is then first created at the experimental crosslink density using an efficient on-lattice method. The CG model is then removed from the lattice and equilibrated using the TIGER2 advanced sampling algorithm. The resulting equilibrated CG system is then reverse-mapped to an all-atom model. The all-atom model is then hydrated in water and equilibrated once more to yield the final predicted structure of the system. The resulting models are validated by comparing with structure-factor plots obtained by neutron scattering and/or X-ray diffraction. The resulting molecular models provide an atomistic-level view of peptide accessibility at the hydrogel surface. If low accessibility is encountered for a given design, the molecular models can provide clear direction regarding the cause of the problem and indicate the design changes that should be made to improve the bioactivity of the system.