Research Paper

Two-Dimensional Modeling of Nanomechanical Strains in Healthy and Diseased Single-Cells During Microfluidic Stress Applications

[+] Author and Article Information
Zachary D. Wilson

Reparative Bioengineering Laboratory, Department of Mechanical and Materials Engineering, Portland State University, Portland, OR 97207

Sean S. Kohles1

Reparative Bioengineering Laboratory, Department of Mechanical and Materials Engineering, Portland State University, Portland, OR 97207; Department of Surgery, Oregon Health & Science University, Portland, OR 97239kohles@cecs.pdx.edu


Corresponding author.

J. Nanotechnol. Eng. Med 1(2), 021005 (May 05, 2010) (6 pages) doi:10.1115/1.4001309 History: Received January 29, 2010; Revised February 12, 2010; Published May 05, 2010; Online May 05, 2010

Investigations in cellular and molecular engineering have explored the impact of nanotechnology and the potential for monitoring and control of human diseases. In a recent analysis, the dynamic fluid-induced stresses were characterized during microfluidic applications of an instrument with nanometer and picoNewton resolution as developed for single-cell biomechanics (Kohles, S. S., Nève, N., Zimmerman, J. D., and Tretheway, D. C., 2009, “Stress Analysis of Microfluidic Environments Designed for Isolated Biological Cell Investigations,” ASME J. Biomech. Eng., 131(12), p. 121006). The results described the limited stress levels available in laminar, creeping-flow environments, as well as the qualitative cellular strain response to such stress applications. In this study, we present a two-dimensional computational model exploring the physical application of normal and shear stress profiles (with 0.1, 1.0, and 10.0 Pa peak amplitudes) potentially available within uniform and extensional flow states. The corresponding cellular strains and strain patterns were determined within cells modeled with healthy and diseased mechanical properties (5.0–0.1 kPa moduli, respectively). Strain energy density results integrated over the volume of the planar section indicated a strong mechanical sensitivity involving cells with disease-like properties. In addition, ex vivo microfluidic environments creating in vivo stress states would require freestream flow velocities of 2–7 mm/s. Knowledge of the nanomechanical stresses-strains necessary to illicit a biologic response in the cytoskeleton and cellular membrane will ultimately lead to refined mechanotransduction relationships.

Copyright © 2010 by American Society of Mechanical Engineers
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Figure 1

Schematics of the microchannel arrangements creating (a) uniform and (b) extensional flow states (10)

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Figure 2

Modeled stress patterns applied to suspended cells in microfluidic environments of (a) uniform and (b) extensional flows with peak stresses similar to monolayer studies (∼1 Pa). Previous experimental creeping laminar flows in these environments created stress patterns with peak values approximately two orders of magnitude lower (∼70 mPa). The planar polar coordinates (r=1.0 a and θ) are defined in the x-y plane at z=0.

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Figure 3

Strain superposition within a modeled cellular section (20 μm diameter with a 0.5 kPa modulus) due to the applied hydrodynamic stresses (1.0 Pa amplitude) potentially available in straight or open (a, b, c sequence) and cross-junction (d, e, f sequence) microfluidic channel configurations. Normal stress-induced strains in tension or compression (a and d) plus shear-induced strains (b and e) equals the total cellular strain state (c and f), where arrow length represents magnitude.

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Figure 4

The relationship between SED integrated over the cell’s sectioned volume due to a range of cellular elastic moduli. Applied extensional and uniform stress conditions with (a) 0.1 Pa, (b) 1.0 Pa, and (c) 10.0 Pa in amplitude are shown. For each order of magnitude increase in applied stress, the integrated SED increases by two orders of magnitude with similar curve shapes.




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