Coupling between electrical and mechanical phenomena is a universal feature of all biological systems. Yet, not much is known about origins of biological electromechanical phenomena on the cellular and subcellular scale. Understanding the underlying molecular mechanisms may have tremendous impact on general understanding of biological processes and specific biomedical applications. Electromechanical stimulation of cells can become a valuable tool for their characterization and can eventually result in the development of novel therapeutic interventions. Insufficient information about electromechanical phenomena in biological systems is a result of the lack of characterization techniques capable of providing such information on the nanometer scale and capable of operation in liquid environment. Recently, piezoresponse force microscopy (PFM) has demonstrated potential for imaging structure of connective and calcified tissues with sub-10 nm resolution. Members of this team have also demonstrated high resolution piezoresponse imaging of model systems in aqueous solutions. The ability to map electromechanical properties in aqueous media opens the way to characterization of biological systems in native-like conditions. Here we propose to expand PFM for characterization and stimulation of live cells in physiological environment. Our long-term vision is to use electromechanical imaging as a diagnostic tool and ultimately, utilize electromechanical stimulation for induction of a desirable change in cell behavior. More specifically, we will focus on electromechanical properties of vascular smooth muscle cells as a model system. To accomplish the goals of this project, we will use electron-beam induced etching to fabricate shielded probes needed for PFM imaging in electrolyte solutions with physiological concentrations. We will perform PFM imaging of live VSMCs in aqueous media and compare piezoresponce of their synthetic and contractile phenotypes. As a result of this project we expect to develop experimental technique needed for investigation of local electromechanical phenomena in live cells and create a methodology for predicting cell behavior upon electromechanical stimulation. Public Health Relevance Statement: Electromechanical imaging of live cells can become a unique method to provide information about electrophysiological response of cells and tissues on the nanoscale. It can also be used in the future for diagnostic purposes. Even more broadly, it is envisioned that the use of electromechanical stimulations of live cells can find applications in tissue engineering, medical diagnosis, and biosensing.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21RR024449-02
Application #
7777889
Study Section
Special Emphasis Panel (ZRR1-BT-B (01))
Program Officer
Friedman, Fred K
Project Start
2009-03-01
Project End
2012-02-28
Budget Start
2010-03-01
Budget End
2011-02-28
Support Year
2
Fiscal Year
2010
Total Cost
$183,026
Indirect Cost
Name
Clemson University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
042629816
City
Clemson
State
SC
Country
United States
Zip Code
29634
Roberts, N A; Noh, J H; Lassiter, M G et al. (2012) Synthesis and electroplating of high resolution insulated carbon nanotube scanning probes for imaging in liquid solutions. Nanotechnology 23:145301
Thompson, G L; Reukov, V V; Nikiforov, M P et al. (2012) Electromechanical and elastic probing of bacteria in a cell culture medium. Nanotechnology 23:245705
Nikiforov, M P; Thompson, G L; Reukov, V V et al. (2010) Double-layer mediated electromechanical response of amyloid fibrils in liquid environment. ACS Nano 4:689-98
Noh, Joo Hyon; Nikiforov, Maxim; Kalinin, Sergei V et al. (2010) Nanofabrication of insulated scanning probes for electromechanical imaging in liquid solutions. Nanotechnology 21:365302
Nikiforov, M P; Reukov, V V; Thompson, G L et al. (2009) Functional recognition imaging using artificial neural networks: applications to rapid cellular identification via broadband electromechanical response. Nanotechnology 20:405708