Abstract
Cell mechanics play a key role in several fundamental biological processes, such as migration, proliferation, differentiation and tissue morphogenesis. In addition, many diseased conditions of the cell are correlated with altered cell mechanics, as in the case of cancer progression. For this there is much interest in methods that can map mechanical properties with a sub-cell resolution. Here, we demonstrate an inverted pulsed opto-acoustic microscope (iPOM) that operates in the 10 to 100 GHz range. These frequencies allow mapping quantitatively cell structures as thin as 10 nm and resolving the fibrillar details of cells. Using this non-invasive all-optical system, we produce high-resolution images based on mechanical properties as the contrast mechanisms, and we can observe the stiffness and adhesion of single migrating stem cells. The technique should allow transferring the diagnostic and imaging abilities of ultrasonic imaging to the single-cell scale, thus opening new avenues for cell biology and biomaterial sciences.
Highlights
Cell mechanics play a key role in several fundamental biological processes, such as migration, proliferation, differentiation and tissue morphogenesis
Acoustic microscopy has allowed measuring the mechanical properties at 1 GHz with a 3 mm axial resolution[19] and the evaluation of their adhesion
In 1984, a time-resolved opto-acoustic technique called picosecond ultrasonics (PU)[20] was developed that could implement frequencies up to a few THz thanks to the thermoelastic expansion induced by the absorption of femtosecond laser pulses
Summary
We demonstrate an inverted pulsed opto-acoustic microscope (iPOM) that operates in the 10 to 100 GHz range These frequencies allow mapping quantitatively cell structures as thin as 10 nm and resolving the fibrillar details of cells. Using this non-invasive all-optical system, we produce high-resolution images based on mechanical properties as the contrast mechanisms, and we can observe the stiffness and adhesion of single migrating stem cells. When reaching back the bottom of the titanium film after reflection, the acoustic strain pulse is monitored by the optical-probe pulses emitted from the second laser using elasto-optic coupling (see Methods) This procedure is equivalent to a GHz percussion at the bottom of the metal film to evaluate the mechanical properties of the cell cultured on the opposite side at a nanoscale.
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