CAREER: Chemomechanical imaging and engineering of single cell phenotype

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Krystyn J. VanVliet0644846The overall objective of this research is to address an unresolved bioengineering challenge: Can we engineer cell phenotype to human advantage through identification, imaging, and control of interactions between the dynamic cell surface and adjacent material environment? This question is central to synthesis of functional tissue in vitro and in vivo. Stem and progenitor cells, defined in part by the ability to adopt several distinct phenotypes under environmental cues, are particularly advantageous targets of this engineered function. Current limitations are due in part to our poor understanding of the general mechanisms by which cells respond dynamically to the environment. The capacity to assess cell phenotype through cell surface characteristics is critical to the engineering of environments that will guide cell function, particularly in mechanically responsive systems such as the vasculature. Thus, the objective of this research is to develop a chemomechanical approach to map the real-time changes in the surface of individual (1) vascular endothelial and (2) adult bone marrow-derived mesenchymal stem cells using an advanced technique of scanning probe microscopy, termed functionalized force imaging (FFI). Sequential image acquisition will enable real-time, in vitro analysis of ligand-binding kinetics and cell response. The capacity to identify and quantify in real-time the molecular basis of cell surface environment interaction mechanisms within individual living cells will provide a new means by which cells present in low frequency can be identified, isolated, and analyzed in response to environmental stimuli. The educational and societal goals of this proposal are integrated within the proposed research methods and applications. The PI will train future researchers by developing new undergraduate laboratory modules and actively participating outreach programs.