Viscoelastic Characterization of Multicellular Tissues in Physiologically Relevant Conditions through Probe Indentation

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This award will produce new knowledge about the mechanical behavior of cancer tissues. Specifically, microscopic measurements of mechanical behavior will be made as the disease progresses. In this project, the focus will be on skin cancers. However, the findings will be applicable to other diseases for which tissues undergo mechanical changes such as arteriosclerosis. The project will deliver the new methods and sensors capable of use in the native liquid environment of biological materials. Establishing a link between cancer progression and mechanical changes in tissues could ultimately have applications to human health. For example, the results of this work could enable the development of patient-specific disease databases, and standards for mechanical tissue behaviors. These might eventually allow classification by individual patient history and information. This could have a transformative effect on medicine and biology research, as mechanical information is not yet broadly considered, much less classified in engineering terms. This research involves several disciplines, including medicine, biology, materials science and mechanical engineering. The multi-disciplinary approach will help broaden participation of underrepresented groups in research and positively impact engineering education. Biological materials are viscoelastic and may respond according to multiple characteristic timescales which are generally not captured in existing mechanical characterization methods, especially micro- and nanoscale approaches. Such methods often reduce the mechanical response to elastic quantities, such as the Young’s modulus, or combinations of a few quantities that empirically combine dissipative and elastic behaviors. This project will develop viscoelastic property inversion methods, whereby the sample is probed using a microscale indenter, and the measured response is translated into a generalized viscoelastic model containing an arbitrary number of characteristic times. This approach will allow quantification of material behaviors in engineering units, which will allow comparison of different specimens measured on different instruments by different researchers. The project also includes development of the indentation apparatus, which will resemble an atomic force microscope, but will be tailored to the typical relaxation timescales observed in biological materials, which are significantly larger than those probed by commercial atomic force microscopes. The project will involve computational and analytical modeling of the fluid dynamics surrounding the probe and sample to incorporate corrections due to fluid forces, which can in some cases obscure the probe-sample interactions for soft materials. Finally, the new apparatus and methods will be employed to acquire the viscoelastic signature of melanoma cancer and healthy skin cell lines.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.