Journal of Biomechanics 34 (2001) 1545–1553 Endothelial, cardiac muscle and skeletal muscle exhibit different viscous and elastic properties as determined by atomic force microscopy Anshu B. Mathur a , Amy M. Collinsworth a , William M. Reichert a , William E. Kraus b , George A. Truskey a, * a Center for Cellular and Biosurface Engineering, Department of Biomedical Engineering,DukeUniversity, Box 90281, 136 Hudson Hall, Durham, NC 27708-0281, USA b Division of Cardiology, Departments of Medicine and Cell Biology, Duke University, Durham, NC 27708-0281, USA Accepted 18 July 2001 Abstract This study evaluated the hypothesis that, due to functional and structural differences, the apparent elastic modulus and viscous behavior of cardiac and skeletal muscle and vascular endothelium would differ. To accurately determine the elastic modulus, the contribution of probe velocity, indentation depth, and the assumed shape of the probe were examined. Hysteresis was observed at high indentation velocities arising from viscous effects. Irreversible deformation was not observed for endothelial cells and hysteresis was negligible below 1 mm/s. For skeletal muscle and cardiac muscle cells, hysteresis was negligible below 0.25 mm/s. Viscous dissipation for endothelial and cardiac muscle cells was higher than for skeletal muscle cells. The calculated elastic modulus was most sensitive to the assumed probe geometry for the first 60nm of indentation for the three cell types. Modeling the probe as a blunt cone–spherical cap resulted in variation in elastic modulus with indentation depth that was less than that calculated by treating the probe as a conical tip. Substrate contributions were negligible since the elastic modulus reached a steady value for indentations above 60nm and the probe never indented more than 10% of the cell thickness. Cardiac cells were the stiffest (100.3710.7kPa), the skeletal muscle cells were intermediate (24.773.5kPa), and the endothelial cells were the softest with a range of elastic moduli (1.470.1to6.870.4kPa) depending on the location of the cell surface tested. Cardiac and skeletal muscle exhibited nonlinear elastic behavior. These passive mechanical properties are generally consistent with the function of these different cell types. r 2001 Elsevier Science Ltd. All rights reserved. Keywords: Elastic modulus; Mechanical properties; Hysteresis; Indenter geometry; Probe velocity 1. Introduction The relationship between cell function and mechan- ical stresses are important for the in vitro design of blood vessels, heart valves, and even whole hearts (Lysaght et al., 1998). Cardiac muscle, skeletal muscle, and endothelial cells have different cytoskeletal arrange- ments to accommodate for the specialized role they play in their resident tissues. Muscle cells are principally involved in contraction. Correspondingly, they have a highly organized system of actin and myosin filaments organized parallel to the long axis of the cell. The endothelium maintains hemostasis, serves as a perme- ability barrier and regulates leukocyte adhesion. While endothelial cells can sense and transduce stresses (Davies, 1995), their primary function is not mechanical and their cytoskeleton is less organized. The mechanical properties of the cell, in turn, depend upon the cytoskeleton and its organization. In general, the behavior of these cells is viscoelastic (Sato et al., 1990; Tagawa et al., 1997). Since the elastic and viscous properties of the cells influence the response of these cells to applied stress, it is critical to understand the mechanical behavior of cells in response *Corresponding author. Tel.: +1-919-660-5147; fax: +1-919-684- 4488. E-mail address: gtruskey@acpub.duke.edu (G.A. Truskey). 0021-9290/01/$-see front matter r 2001 Elsevier Science Ltd. All rights reserved. PII:S0021-9290(01)00149-X