Bacterial cell division takes place in three phases: Z-ring formation at midcell, followed by divisome assembly and building of the septum per se. Using time-lapse microscopy of live bacteria and a high-precision cell edge detection method, we have previously found the true time for the onset of septation, τ _c , and the time between consecutive divisions, τ _g . Here, we combine the above method with measuring the dynamics of the FtsZ-GFP distribution in individual Escherichia coli cells to determine the Z-ring positioning time, τ _z . To analyze the FtsZ-GFP distribution along the cell, we used the integral fluorescence profile (IFP), which was obtained by integrating the fluorescence intensity across the cell width. We showed that the IFP may be approximated by an exponential peak and followed the peak evolution throughout the cell cycle, to find a quantitative criterion for the positioning of the Z-ring and hence the value o...

Micro-RNAs (miRNAs) play a crucial role in post-transcriptional gene regulation by pairing with target mRNAs to repress protein production. It has been shown that over one-third of human genes are targeted by miRNA. Although hundreds of miRNAs have been identified in mammalian genomes, the function of miRNA-based repression in the context of gene regulation networks still remains unclear. In this study, we explore the functional roles of feedback regulation by miRNAs. In a model where repression of translation occurs by sequestration of mRNA by miRNA, we find that miRNA and mRNA levels are anti-correlated, resulting in larger fluctuation in protein levels than theoretically expected assuming no correlation between miRNA and mRNA levels. If miRNA repression is due to a catalytic suppression of translation rates, we analytically show that the protein fluctuations can be strongly repressed with miRNA regulation. We also discuss how either of these modes may be relevant for cell func...

How cell collectives move and deposit subunits within a developing embryo is a question of outstanding interest. In many cases, a chemotactic mechanism is employed, where cells move up or down a previously generated attractive or repulsive gradient of signalling molecules. Recent studies revealed the existence of systems with isotropic chemoattractant expression in the lateral line primordium of zebrafish. Here we propose a mechanism for a cell collective, which actively modulates an isotropically expressed ligand and encodes an initial symmetry breaking in its velocity. We derive a closed solution for the velocity and identify an optimal length that maximizes the tissues' velocity. A length dependent polar gradient is identified, its use for pro-neuromast deposition is shown by simulations and a critical time for cell deposition is derived. Experiments to verify this model are suggested.

A frequently neglected aspect of protein–protein interactions is flexibility. Small-scale fluctuations are present even in globular proteins, and alternative conformations can have a significant influence on the binding process. However, flexibility becomes highly prominent in complexes involving intrinsically disordered proteins. The importance of disordered regions in protein interactions has been recognized only relatively recently. In this survey we examine the basic properties of the complexes of disordered and ordered proteins from three different directions. The comparison of the interface properties shows that although disordered proteins can also adopt well-defined conformations in their bound form, their inherently dynamic nature is cast into their complexes. Furthermore, an overview of prediction methods indicates that disordered proteins as well as their binding regions can be recognized from the amino acid sequence by capturing the basic biophysical properties of the...

Asexual reproduction in multicellular organisms is a complex biophysical process that is not yet well understood quantitatively. Here, we report a detailed population study for the asexual freshwater planarian Schmidtea mediterranea, which can reproduce via transverse fission due to a large stem cell contingent. Our long-term observations of isolated non-interacting planarian populations reveal that the characteristic fission waiting time distributions for head and tail fragments differ significantly from each other. The stochastic fission dynamics of tail fragments exhibits non-negligible memory effects, implying that an accurate mathematical description of future data should be based on non-Markovian tree models. By comparing the effective growth of non-interacting planarian populations with those of self-interacting populations, we are able to quantify the influence of interactions between flatworms and physical conditions on the population growth. A surprising result i...

To adhere and migrate, cells generate forces through the cytoskeleton that are transmitted to the surrounding matrix. While cellular force generation has been studied on 2D substrates, less is known about cytoskeletal-mediated traction forces of cells embedded in more in vivo-like 3D matrices. Recent studies have revealed important differences between the cytoskeletal structure, adhesion, and migration of cells in 2D and 3D. Because the cytoskeleton mediates force, we sought to directly compare the role of the cytoskeleton in modulating cell force in 2D and 3D. MDA-MB-231 cells were treated with agents that perturbed actin, microtubules, or myosin, and analyzed for changes in cytoskeletal organization and force generation in both 2D and 3D. To quantify traction stresses in 2D, traction force microscopy was used; in 3D, force was assessed based on single cell-mediated collagen fibril reorganization imaged using confocal reflectance microscopy. Interestingly, even though pre...

The importance of the tumor microenvironment in cancer progression is undisputed, yet the significance of biophysical forces in the microenvironment remains poorly understood. Interstitial fluid flow is a nearly ubiquitous and physiologically relevant biophysical force that is elevated in tumors because of tumor-associated angiogenesis and lymphangiogenesis, as well as changes in the tumor stroma. Not only does it apply physical forces to cells directly, but interstitial flow also creates gradients of soluble signals in the tumor microenvironment, thus influencing cell behavior and modulating cell–cell interactions. In this paper, we highlight our current understanding of interstitial fluid flow in the context of the tumor, focusing on the physical changes that lead to elevated interstitial flow, how cells sense flow and how they respond to changes in interstitial flow. In particular, we emphasize that interstitial flow can directly promote tumor cell invasion through a mechanism...

The translation of cellular mRNA to protein is a tightly controlled process often deregulated in diseases such as cancer. Furthering our understanding of mRNA structural elements and the intracellular proteins and signaling pathways that affect protein expression is crucial in the development of new therapies. In this review, we discuss the current state-of-the-art of detecting and determining the role of mRNA sequence elements in regulating the initiation of mRNA translation and the therapeutic strategies that exploit this knowledge to treat disease.