Dylan Wootton, University of Utah
Myocardial Infarctions (MIs, commonly known as heart attacks) affect 16 million people every year. After an MI, proper cardiac tissue remodeling is necessary to deter heart failure. Matrix Metalloproteases (MMPs) play a crucial role in proper extracellular matrix (ECM) remodeling, and as a result, their concentration greatly impacts clinical outcomes of MI recovery. One method to control MMP concentration is through the use of synthetic biology. Synthetic biology is a novel field that utilizes genetic constructs (promoters, operators, coding sequences, and repressors) to alter levels of protein expression depending on the chemical inputs a cell is exposed to. To dynamically control MMP concentration to influence ECM remodeling, we are interfacing biomaterials and synthetic biology to create an MMP-responsive biomaterial which, upon exposure to MMP, is predicted to activate a mammalian genetic module that alters MMP and MMP inhibitor concentrations. In this experiment, several MMP-responsive materials were produced in bacteria. Growth and induction conditions that influence biomaterial production were characterized, and an optimal growth protocol was determined. Given the propensity for the biomaterial to be expressed in inclusion bodies, an additional extraction method was determined. Following production of this biomaterial, material response to MMP activity was assayed using Western Blot analysis. Further work will focus on the ability of the materials to activate a mammalian genetic module, and the subsequent use of this module to influence MMP concentration.