Measuring Cell Viscoelastic Properties Using a Microfluidic Extensional Flow Device.
The quantification of cellular mechanical properties is of tremendous interest in biology and medicine. Recent microfluidic technologies that infer cellular mechanical properties based on analysis of cellular deformations during microchannel traversal have dramatically improved throughput over traditional single-cell rheological tools, yet the extraction of material parameters from these measurements remains quite complex due to challenges such as confinement by channel walls and the domination of complex inertial forces. Here, we describe a simple microfluidic platform that uses hydrodynamic forces at low Reynolds number and low confinement to elongate single cells near the stagnation point of a planar extensional flow. In tandem, we present, to our knowledge, a novel analytical framework that enables determination of cellular viscoelastic properties (stiffness and fluidity) from these measurements. We validated our system and analysis by measuring the stiffness of cross-linked dextran microparticles, which yielded reasonable agreement with previously reported values and our micropipette aspiration measurements. We then measured viscoelastic properties of 3T3 fibroblasts and glioblastoma tumor initiating cells. Our system captures the expected changes in elastic modulus induced in 3T3 fibroblasts and tumor initiating cells in response to agents that soften (cytochalasin D) or stiffen (paraformaldehyde) the cytoskeleton. The simplicity of the device coupled with our analytical model allows straightforward measurement of the viscoelastic properties of cells and soft, spherical objects.
Hydrodynamics Laboratory, CNRS UMR7646, Department of Mechanics, École Polytechnique, Palaiseau, France.
Lionel
L
Guillou
Department of Bioengineering, UC Berkeley, Berkeley, California; Department of Chemical and Biomolecular Engineering, UC Berkeley, Berkeley, California.
Joanna B
JB
Dahl
Department of Bioengineering, UC Berkeley, Berkeley, California; The UC Berkeley-UCSF Graduate Program in Bioengineering, UC Berkeley, Berkeley, California.
Jung-Ming G
JG
Lin
Hydrodynamics Laboratory, CNRS UMR7646, Department of Mechanics, École Polytechnique, Palaiseau, France.
AbduI I
AI
Barakat
Hydrodynamics Laboratory, CNRS UMR7646, Department of Mechanics, École Polytechnique, Palaiseau, France.
Julien
J
Husson
Department of Chemical and Biomolecular Engineering, UC Berkeley, Berkeley, California.
Susan J
SJ
Muller
Department of Bioengineering, UC Berkeley, Berkeley, California; Department of Chemical and Biomolecular Engineering, UC Berkeley, Berkeley, California; The UC Berkeley-UCSF Graduate Program in Bioengineering, UC Berkeley, Berkeley, California. Electronic address: skumar@berkeley.edu.
Sanjay
S
Kumar
D000818:Animals; D001696:Biomechanical Phenomena; D045744:Cell Line, Tumor; D004548:Elasticity; D005909:Glioblastoma / Q000473:pathology; D056656:Lab-On-A-Chip Devices; D051379:Mice; D041681:NIH 3T3 Cells; D014783:Viscosity