A lesson from earthquake engineering for selectively damaging cancer cell structures.

The progressive falling of barriers among disciplines is opening unforeseen scenarios in diagnosis and treatment of cancer diseases. By sharing models and mature knowledge in physics, engineering, computer sciences and molecular biology, synergistic efforts have in fact contributed in the last years to re-think still unsolved problems, shedding light on key roles of mechanobiology in tumors and envisaging new effective strategies for a precise medicine. The use of ultrasounds for altering cancer cells' program is one of the most attracting grounds to be explored in oncophysics, although how to administer mechanical energy to impair selected cell structures and functions simultaneously overcoming the critical trade-off between the impact of the cure and the patient risk still remains an open issue. Within this framework, by starting from the theoretical possibility of selectively attacking malignant cells by exploiting the stiffness discrepancies between tumor and healthy single cells, first proposed by Fraldi et al. (2015), we here investigate the in-frequency response of an overall spherical close-packing of geometrically equal polyhedral cells to gain insights into how mechanical resonance and vibration-induced failure phenomena can be oriented to destroy specific target units when both the cell populations coexist, as it happens for in vivo cases. Inspired by the dynamic action of earthquakes - which fracture only selected elements among adjacent ones in the same structure or damage individual constructions in contiguous buildings - we study the harmonic response of hierarchically architectured cell agglomerates, inhabited by both tumor and healthy cells that interact mutually throughout the extra-cellular matrix and whose cytoskeleton is modeled as a nonlinear soft-tensegrity structure. Numerical Finite Element results show that, at frequencies compatible with low intensity therapeutic ultrasounds, mechanical resonance and possible fatigue cycles of the pre-stressed actin filaments and microtubules can be selectively induced in cancer cells as a function of the global volume fraction of the cell species, paving the way for future engineered treatment protocols.