Mechanical properties of normal versus cancerous breast cells.
A cell's mechanical properties are important in determining its adhesion, migration, and response to the mechanical properties of its microenvironment and may help explain behavioral differences between normal and cancerous cells. Using fluorescently labeled peroxisomes as microrheological probes, the interior mechanical properties of normal breast cells were compared to a metastatic breast cell line, MDA-MB-231. To estimate the mechanical properties of cell cytoplasms from the motions of their peroxisomes, it was necessary to reduce the contribution of active cytoskeletal motions to peroxisome motion. This was done by treating the cells with blebbistatin, to inhibit myosin II, or with sodium azide and 2-deoxy-D-glucose, to reduce intracellular ATP. Using either treatment, the peroxisomes exhibited normal diffusion or subdiffusion, and their mean squared displacements (MSDs) showed that the MDA-MB-231 cells were significantly softer than normal cells. For these two cell types, peroxisome MSDs in treated and untreated cells converged at high frequencies, indicating that cytoskeletal structure was not altered by the drug treatment. The MSDs from ATP-depleted cells were analyzed by the generalized Stokes-Einstein relation to estimate the interior viscoelastic modulus G* and its components, the elastic shear modulus G' and viscous shear modulus G", at angular frequencies between 0.126 and 628 rad/s. These moduli are the material coefficients that enter into stress-strain relations and relaxation times in quantitative mechanical models such as the poroelastic model of the interior regions of cancerous and non-cancerous cells.
Department of Biochemistry and Molecular Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
Amanda M
AM
Smelser
Department of Biochemistry and Molecular Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.|Department of Physics, Wake Forest University, Winston-Salem, NC, 27109, USA.
Jed C
JC
Macosko
Department of Physics, Wake Forest University, Winston-Salem, NC, 27109, USA.
Adam P
AP
O'Dell
Department of Physics, Wake Forest University, Winston-Salem, NC, 27109, USA.
Scott
S
Smyre
Department of Physics, Wake Forest University, Winston-Salem, NC, 27109, USA.
Keith
K
Bonin
Department of Physics, Wake Forest University, Winston-Salem, NC, 27109, USA. gholz@wfu.edu.
George
G
Holzwarth
D001940:Breast / Q000166:cytology / Q000502:physiology*; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology*; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D003198:Computer Simulation; D055119:Elastic Modulus / Q000502:physiology; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000502:physiology*; D020675:Peroxisomes / Q000502:physiology; D013314:Stress, Mechanical; D013718:Tensile Strength / Q000502:physiology; D059016:Tumor Microenvironment / Q000502:physiology*; D014783:Viscosity
D020409:Molecular Motor Proteins
Actin; Brownian motion; Cytoskeleton; GSE; Particle tracking; Peroxisomes