Microrheology of responsive hydrogels

Self-assembling hydrogels are an emerging class of materials that has received growing interest from the pharamaceutical and biomedical fields. Hydrogels have become exciting candidates for use in drug delivery and tissue engineering applications because of their unique combination of biological compatibility and responsive mechanical behavior. Successful engineering of these materials relies on establishing a relationship between the self-assembly mechanism, resulting microstructure, and final rheological properties.;This dissertation focuses on passive microrheology to characterize transient and equilibrated structural and mechanical properties of self-assembling hydrogels. Passive microrheology uses the thermal motion of embedded, micrometerdiameter particles to locally probe the material and extract rheological and structural information. Microrheology compliments bulk rheology in studies of soft materials, with advantages that include exquisite sensitivity for low modulus materials, large frequency range, no applied external force, rapid data acquisition, and small required sample volumes.;Characterization of the liquid-solid transition in hydrogelators relies on defining gelation properties such as the gel point and the critical scaling exponents. The gel point provides a reference by which to define gelation, while the critical scaling exponents offer insight into the nature of network interconnectivity. Using the principles of time-cure superposition and theoretical scaling relationships for near-critical gels, we develop a rigorous method for determining these values directly from microrheological measurements.;A comprehensive analysis of localization error associated with video microscopy particle tracking microrheology validates our method and illustrates how the presence of error can either make time-cure superposition impossible or dramatically affect the values of the gel point and critical exponents. Heuristics are provided for minimizing sources of error to avoid potential misinterpretations of the results.;We use time-cure superposition microrheology and our understanding of error to compare the gelation kinetics of four synthetic peptide hydrogelators that differ in sequence by a single point amino acid substitution. We study the effect of concentration, ionic strength, and temperature on the energetics of self-assembly and ultimately show that the gelation kinetics of the peptide hydrogelators can be predictably altered through peptide design when the forces that drive gelation are well understood.;To provide a theoretical basis for the change in gelation kinetics with peptide sequence and total peptide charge, a simplified electrostatic double layer model is developed that accounts for intra- and intermolecular electrostatic interactions that occur during self-assembly. Interaction potentials are calculated and used to determine critical gel times, which agree semi-quantitatively with microrheology results.;Finally, we utilize another passive microrheology technique, diffusing wave spectroscopy, to investigate the high-frequency viscoelastic response of self-assembling biopolymer hydrogels under nonequilibrium conditions. The addition of a network-activating motor protein and a network-crosslinking protein allows us to study the competitive mechanisms employed by cells to modify the rheology of their cytoplasmic environment. The observed response is shown to be dependent on the average distance between filament-bound motor proteins and the length-scale-dependent bending rigidity of the polymer filaments, with the transition between effective persistence lengths marked by a characteristic crossover length. For separation distances greater than the bare persistence length and below the crossover length, the response is dominated by transverse filament fluctuations, while at separation distances shorter than the persistence length and above the crossover length, the filaments are characterized by a reduced effective persistence length and higher effective temperature. Crosslinks are shown to recover the bare persistence length by reducing the length scale over which particle motion is sensitive to motor activity until it is smaller than the crossover length.;Overall, this work expands the application of microrheology to characterize the gelation process and equilibrium properties of new and emerging selfassembling soft materials that are currently being engineered for future therapeutic applications.