Destruction of cancer cells by laser-induced shock waves: recent developments in experimental treatments and multiscale computer simulations.

In this emerging area article we review recent progress in the mechanical destruction of cancer cells using laser-induced shock waves. The pure mechanical damaging and destruction of cancer cells associated with this technique possibly opens up a new route to tumor treatments and the corresponding therapies. At the same time progress in multiscale simulation techniques makes it possible to simulate mechanical properties of soft biological matter such as membranes, cytoskeletal networks and even whole cells and tissue. In this way an interdisciplinary approach to understanding key mechanisms in shock wave interactions with biological matter has become accessible. Mechanical properties of biological materials are also critical for many physiological processes and cover length scales ranging from the atomistic to the macroscopic scale. We argue that the latest developments and progress in experimentation enable the investigation of the shock wave interaction with cancer cells on multiple time- and length-scales. In this way the integrated use of experiment and simulation can address key challenges in this field. The exploration of the biological effects of laser-generated shock waves on a fundamental level constitutes an emerging multidisciplinary research area combining scientific methods from the areas of physics, biology, medicine and computer science.

Characterization of a setup to test the impact of high-amplitude pressure waves on living cells.

The impact of pressure waves on cells may provide several possible applications in biology and medicine including the direct killing of tumors, drug delivery or gene transfection. In this study we characterize the physical properties of mechanical pressure waves generated by a nanosecond laser pulse in a setup with well-defined cell culture conditions. To systematically characterize the system on the relevant length and time scales (micrometers and nanoseconds) we use photon Doppler velocimetry (PDV) and obtain velocity profiles of the cell culture vessel at the passage of the pressure wave. These profiles serve as input for numerical pressure wave simulations that help to further quantify the pressure conditions on the cellular length scale. On the biological level we demonstrate killing of glioblastoma cells and quantify experimentally the pressure threshold for cell destruction.

Influence of molecular noise on the growth of single cells and bacterial populations.

During the last decades experimental studies have revealed that single cells of a growing bacterial population are significantly exposed to molecular noise. Important sources for noise are low levels of metabolites and enzymes that cause significant statistical variations in the outcome of biochemical reactions. In this way molecular noise affects biological processes such as nutrient uptake, chemotactic tumbling behavior, or gene expression of genetically identical cells. These processes give rise to significant cell-to-cell variations of many directly observable quantities such as protein levels, cell sizes or individual doubling times. In this study we theoretically explore if there are evolutionary benefits of noise for a growing population of bacteria. We analyze different situations where noise is either suppressed or where it affects single cell behavior. We consider two specific examples that have been experimentally observed in wild-type Escherichia coli cells: (i) the precision of division site placement (at which molecular noise is highly suppressed) and (ii) the occurrence of noise-induced phenotypic variations in fluctuating environments. Surprisingly, our analysis reveals that in these specific situations both regulatory schemes [i.e. suppression of noise in example (i) and allowance of noise in example (ii)] do not lead to an increased growth rate of the population. Assuming that the observed regulatory schemes are indeed caused by the presence of noise our findings indicate that the evolutionary benefits of noise are more subtle than a simple growth advantage for a bacterial population in nutrient rich conditions.