7th Annual Symposium
Physics of Cancer
October 4-6, 2016
|PoC - Physics of Cancer - Annual Symposium|
Probing the Physical Properties of the Microenvironment Niche
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute (NIH), Bethesda, MD 20892-4256, U.S.A.
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Tissue microenvironment is composed of heterogeneous biological components and physical parameters, and nanometric topography in 3D is one of crucial factors that influence on cell phenotype, tissue morphogenesis and cancer progression. . Here we aim to distinguish the contributions of the physical from those due to chemical properties on cell fate as it relates to malignancy and normal tissue homeostasis. However, delineating the complex interplay between cells and their physical microenvironment is challenging using current techniques. What is needed is the ability to resolve and quantitate minute forces that cells sense in the local environment (on the order of microns) within thick tissue (in mm). 3D culture models approximate in vivo architecture and signaling cues, allowing for real time characterization of cell-ECM dynamics. We employ two approaches where we recreate diverse nanoscale topographies of protein distributions in 3D matrix for the purpose of mimicking tissue microenvironment. To achieve this, we chemically immobilize the proteins on the surface of magnetic nanoparticles then using an applied magnetic field –to program self-assembly. Using this simple technique, we achieved diverse 3D topography by varying fibril diameter, spacing and localized or interfaced architecture of proteins, and independent of other material parameters of the matrix, such as stiffness. Next, we employ a novel method to quantitate absolute physical properties of tissue. We present active Microrheology by optical trapping in vivo, using in situ calibration to accurately apply and measure forces to quantitate tissue mechanics. With micrometer resolution at broadband frequencies and depths approaching 0.5 mm, aMotiv applies differential stresses and strains on force, time and length scales relevant to cellular processes in living zebrafish. We determined that proxy calibration methods overestimate complex moduli by ~20 fold. While ECM hydrogels displayed rheological properties predicted for polymer networks, new models may be needed to describe the behavior of tissues observed. We believe that this platform can be used in elucidating the basic mechanisms that govern the role of material properties in mechanobiology.