Intracellular Mechanics and Activity of Breast Cancer Cells Correlate with Metastatic Potential

Abstract

Mechanics of cancer cells are directly linked to their metastatic potential, or ability to produce a secondary tumor at a distant site. Metastatic cells survive in the circulatory system in a non-adherent state, and can squeeze through barriers in the body. Such considerable structural changes in cells rely on rapid remodeling of internal structure and mechanics. While external mechanical measurements have demonstrated enhanced pliability of cancer cells with increased metastatic potential, little is known about dynamics of their interior and we expect that to change significantly in metastatic cells. We perform a comparative study, using particle-tracking to evaluate the intracellular mechanics of living epithelial breast cells with varying invasiveness. Particles in all examined cell lines exhibit super-diffusion with a scaling exponent of 1.4 at short lag times, likely related to active transport by fluctuating microtubules and their associated molecular motors. Specifics of probe-particle transport differ between the cell types, depending on the cytoskeleton network-structure and interactions with it. Our study shows that the internal microenvironment of the highly metastatic cells evaluated here is more pliable and their cytoskeleton is less dense than the poorly metastatic and benign cells. We thus reveal intracellular structure and mechanics that can support the unique function and invasive capabilities of highly metastatic cells.

Asymmetry in traction forces produced by migrating preadipocytes is bounded to 33%

“…3 ). This type of distribution is typical for speed distributions in general, and has also been observed in intracellular particle motion [30] .…”

Cell Growth Rate Dictates the Onset of Glass to Fluidlike Transition and Long Time Superdiffusion in an Evolving Cell Colony

“…Previous works have investigated a number of two-dimensional (2D) models in various contexts [9,16,25], including probing the dynamics in a homeostatic state where cell birth-death processes are balanced [26,27]. Existing three-dimensional (3D) models focus solely on tumor growth kinetics, spatial growth patterns [28,29], or on cell migration at low cellular density on timescales shorter than the cell division time [30][31][32]. A recent interesting study [26] shows that cell dynamics in a confluent tissue is always fluidized by cell birth and death processes, on timescales comparable to cell division time.…”

Embryonic stem cells growing in 3-dimensions shift from reliance on the substrate to each other for mechanical support

“…Mechanical loading of cells through the substrate has also been shown to affect cell differentiation and development (Shoham and Gefen, 2012;Shoham et al, 2015), where stiffening of the cells themselves is also related to their function and can indicate disease states such as cancer (Gal and Weihs, 2012;Guck et al, 2005), or response of different cell types to changes in their environments (Poh et al, 2010). Those studies not only supply evidence to the significance of mechano-biology in stem cell development, but also provide important tools for controlling stem cells in vitro.…”