期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：46
页码：E7159-E7168
DOI：10.1073/pnas.1605112113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceCell mechanics is crucial for many, if not all, cell functions. Although mechanics at the scale of the whole cell is extensively documented, there are only few methods to measure intracellular mechanics at the local scale. Here, we develop a technique that allows us (i) to map the spatial variations of intracellular mechanical parameters; (ii) to study how the actin and microtubule cytoskeleton, intracellular membranes, and ATP-dependent active forces contribute to intracellular mechanics; and (iii) to differentiate normal and cancer cells. Because intracellular mechanical maps can detect subtle differences in the spatial distribution of mechanical parameters even in the absence of any change in their average values, our approach could provide a diagnostic and prognostic tool for cancers. The mechanical properties of cells impact on their architecture, their migration, intracellular trafficking, and many other cellular functions and have been shown to be modified during cancer progression. We have developed an approach to map the intracellular mechanical properties of living cells by combining micropatterning and optical tweezers-based active microrheology. We optically trap micrometer-sized beads internalized in cells plated on crossbow-shaped adhesive micropatterns and track their displacement following a step displacement of the cell. The local intracellular complex shear modulus is measured from the relaxation of the bead position assuming that the intracellular microenvironment of the bead obeys power-law rheology. We also analyze the data with a standard viscoelastic model and compare with the power-law approach. We show that the shear modulus decreases from the cell center to the periphery and from the cell rear to the front along the polarity axis of the micropattern. We use a variety of inhibitors to quantify the spatial contribution of the cytoskeleton, intracellular membranes, and ATP-dependent active forces to intracellular mechanics and apply our technique to differentiate normal and cancer cells.
关键词：microrheology ; optical tweezers ; cancer ; viscoelasticity ; cytoskeleton
