Boris Krasovitski, Shy Shoham and Eitan Kimmel (Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel), Victor Frenkel (Catholic Univ). Proceedings of the National Academy of Sciences of the United States of America edited by Robert Langer, Massachusetts Institute of Technology, Cambridge, MA, and approved January 12, 2011
The localized cavity formation and cell rupture observed in these experiments are consistent with an intracellular cavitation mechanism, originating in bilayer sonophores and possibly leading to irreversible alterations in the cells through membrane tears or fatigue/damage…The observed cavities were not limited to the outer membrane and were also seen within intracellular membranes…All and all, we showed in this study that the bilayer membrane is capable of directly transforming acoustic energy into mechanical stresses and strains at the subcellular and cellular level, which do not require a prior existence of air voids in the tissue.
The purpose of this study was to develop a unified model capable of explaining the mechanisms of interaction of ultrasound and biological tissue at both the diagnostic nonthermal, noncavitational (<100 mW·cm−2) and therapeutic, potentially cavitational (>100 mW·cm−2) spatial peak temporal average intensity levels. The cellular-level model combines the physics of bubble dynamics with cell biomechanics to determine the dynamic behavior of the two lipid bilayer membrane leaflets. The existence of such a unified model could potentially pave the way to a number of controlled ultrasound-assisted applications, including central-nervous-system (CNS) modulation and blood–brain barrier permeabilization.
The model predicts that the cellular membrane is intrinsically capable of absorbing mechanical energy from the ultrasound field and transforming it into expansions and contractions of the intramembrane space. It further predicts that the maximum area strain is proportional to the acoustic pressure amplitude and inversely proportional to the square root of the frequency and is intensified by proximity to free surfaces, the presence of nearby microbubbles in free medium, and the flexibility of the surrounding tissue.
Our results support the hypothesis that ultrasonically induced bilayer membrane motion, which does not require preexistence of air voids in the tissue, may account for a variety of bioeffects and could elucidate mechanisms of ultrasound interaction with biological tissue that are currently not fully understood.