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Kaliman, S.

Publications and source records attributed to Kaliman, S..

3 recordsLinked to original sources

Estimation of the mass density of biological matter from refractive index measurements

The quantification of physical properties of biological matter gives rise to novel ways of understanding functional mechanisms by utilizing models that explicitly depend on physical observables. One of the basic biophysical properties is the mass density (MD), which determines the degree of crowdedness. It impacts the dynamics in sub-cellular compartments and further plays a major role in defining the opto-acoustical properties of cells and tissues. As such, the MD can be connected to the refractive index (RI) via the well known Lorentz-Lorenz relation, which takes into account the polarizability of matter. However, computing the MD based on RI measurements poses a challenge as it requires detailed knowledge of the biochemical composition of the sample. Here we propose a methodology on how to account for a priori and a posteriori assumptions about the biochemical composition of the sample as well as respective RI measurements. To that aim, we employ the Biot mixing rule of RIs alongside the assumption of volume additivity to find an approximate relation of MD and RI. We use Monte-Carlo simulations as well as Gaussian propagation of uncertainty to obtain approximate analytical solutions for the respective uncertainties of MD and RI. We validate this approach by applying it to a set of well characterized complex mixtures given by bovine milk and intralipid emulsion. Further, we employ it to estimate the mass density of trunk tissue of living zebrafish (Danio rerio) larvae. Our results enable quantifying changes of mass density estimates based on variations in the a priori assumptions. This illustrates the importance of implementing this methodology not only for MD estimations but for many other related biophysical problems, such as mechanical measurements using Brillouin microscopy and transient optical coherence elastography.

biophysics↗

Capturing the mechanosensitivity of cell proliferation in models of epithelium

Despite the primary role of cell proliferation in tissue development and homeostatic maintenance, the interplay between cell density, cell mechanoresponse, and cell growth and division is not yet understood. In this article we address this issue by reporting on an experimental investigation of cell proliferation on all time- and length-scales of the development of a model tissue, grown on collagen-coated glass or deformable substrates. Through extensive data analysis, we demonstrate the relation between mechanoresponse and probability for cell division, as a function of the local cell density. Motivated by these results, we construct a minimal model of cell proliferation that can recover the data. By parametrizing the growth and the dividing phases of the cell cycle, and introducing such a proliferation model in dissipative particle dynamics simulations, we recover the mechanoresponsive, time-dependent density profiles in 2D tissues growing to macroscopic scales. The importance of separating the cell population into growing and dividing cells, each characterized by a particular time scale, is further emphasized by calculations of density profiles based on adapted Fisher-Kolmogorov equations. Together, these results show that the mechanoresponse on the level of a constitutive cell and its proliferation results in a matrix-sensitive active pressure. The latter evokes massive cooperative displacement of cells in the invading tissue and is a key factor for developing large-scale structures in the steady state.

biophysics↗

On the mechanical regulation of epithelial tissue homeostasis

Despite recent efforts to understand homeostasis in epithelial tissues, there are many unknowns surrounding this steady state. It is considered to be regulated by mechanoresponse, but unlike for single cells, this remains heavily debated for tissues. Here, we show that changes in matrix stiffness induce a non-equilibrium transition from tubular to squamous Madin-Darby Canine Kidney II tissues. Nonetheless, despite different cell morphologies and densities, all homeostatic tissues display equivalent topologies, which, hence, must be actively targeted and regulated. On the contrary, the mechanoresponse induces dramatic changes in the large-scale organization of the colonies. On stiff gels, this yields an unreported cooperative state of motile cells displaying higher densities than in the arrested homeostatic state. This suggests a more complex relation between cell density and motility than previously anticipated. Our results unequivocally relate the mechanosensitive properties of individual cells to the evolving macroscopic structures, an effect that could be important for understanding the emergent pathologies of living tissues.

biophysics↗