HIGH-THROUGHPUT INTRACELLULAR MICRORHEOLOGY: A NEW TOOL FOR CANCER RESEARCH


Year of Award:
2009
Award Type:
R21
Project Number:
CA137686
RFA Number:
RFA-CA-08-006
Technology Track:
Molecular & Cellular Analysis Technologies
PI/Project Leader:
WIRTZ, DENIS
Other PI or Project Leader:
N/A
Institution:
JOHNS HOPKINS UNIVERSITY
Cancer mortality and morbidity are critically related to tumor invasion and metastasis in which the molecular mechanisms are poorly understood. Until their etiology is better revealed, attempts to develop new cancer therapeutics would remain empirical. Cell motility, which drives cancer metastasis, involves dynamic and regulated re-arrangements of the cytoskeleton. Our work and that of several other groups have shown that cytoskeleton phenotypes are typically accompanied by drastic changes in the viscoelastic properties of the cytoskeleton, which in turn modulate the ability of the cytoskeleton to generate net pushing forces at the leading edge and allow the cell to change its shape. Changes in cell mechanical properties have long been predicted to correlate with metastatic potential. However, current cell-mechanics approaches suffer from serious drawbacks - including time of measurement, lack of multiplexing, ambiguity of measurements - which prevent a direct test of this important hypothesis. The objective of this study is to: develop a highly-optimized high-throughput ballistic injection nanorheology (htBIN) technological platform to measure the micromechanical properties in cancer cells rapidly (