BJ Articles Ahead of Print

Tumor cells disseminate to distant organs mainly through blood circulation, in which they experience considerable levels of fluid shear stress. However, the effects of hemodynamic shear stress on biophysical properties and functions of circulating tumor cells in suspension are not fully understood. In this study, we found that the majority of suspended breast tumor cells could be eliminated by fluid shear stress, while cancer stem cells held survival advantages over conventional cancer cells. Compared to untreated cells, tumor cells surviving shear stress exhibited unique biophysical properties: cell adhesion was significantly retarded; these cells exhibited elongated morphology and enhanced spreading and expressed genes related to epithelial-mesenchymal transition or hybrid phenotype; surviving tumor cells showed reduced F-actin assembly and stiffness.

Compaction of T4 phage DNA (166 kbp) by short oligopeptide octamers composed of two types of amino acids, four cationic lysine (K) and four polar non-ionic serine (S) having different sequence order was studied by single-molecule fluorescent microscopy. We found that efficient DNA compaction by oligopeptide octamers depends on the geometrical match between phosphate groups of DNA and cationic amines. The amino acid sequence order in octamers dramatically affects the mechanism of DNA compaction which changes from a discrete all-or-nothing coil-globule transition induced by less efficient (K4S4) octamer to a continuous compaction transition induced by (KS)4 octamer with a stronger DNA-binding character.

One of the central tasks in systems biology is to understand how cells regulate their metabolism. Hierarchical regulation analysis (HRA) is a powerful tool to study this regulation at the metabolic, gene-expression and signaling levels. It has been widely applied to study the steady-state regulation; but analysis of the metabolic dynamics remains challenging because it is difficult to measure time-dependent metabolic flux. Here we develop a non-parametric method that uses Gaussian processes to accurately infer the dynamics of a metabolic pathway based only on metabolite measurements; from this we then go in to obtain a dynamical view of the hierarchical regulation processes invoked over time to control the activity in a pathway.

In eukaryotes, DNA is packaged within nucleosomes. The DNA of each nucleosome is typically centered around an octameric histone protein core: one central tetramer plus two separate dimers. Studying the assembly mechanisms of histones is essential for understanding the dynamics of entire nucleosomes and higher-order DNA packaging. Here, we investigate canonical histone assembly and that of the centromere-specific histone variant, centromere protein A (CENP-A), using molecular dynamics simulations.

Upon contact with antigen presenting cells (APCs) cytotoxic T lymphocytes (T cells) establish a highly organized contact zone denoted as immunological synapse (IS). The formation of the IS implies relocation of the microtubule organizing center (MTOC) towards the contact zone, which necessitates a proper connection between MTOC and IS via dynamic microtubules (MTs). The efficiency of the MTs finding the IS within relevant time scale is, however, still illusive. We investigate how MTs search the three-dimensional constrained cellular volume for the IS and bind upon encounter to dynein anchored at the IS cortex.

For over 20 years, genetically encoded Ca2+ indicators have illuminated dynamic Ca2+ signaling activity in living cells and, more recently, whole organisms. We are just now beginning to understand how they work. Various fluorescence colors of these indicators have been developed, including red. Red ones are promising because longer wavelengths of light scatter less in tissue, making it possible to image deeper. They are engineered from a red fluorescent protein that is circularly permuted and fused to a Ca2+ sensing domain.

Cells grow, move, and respond to outside stimuli by large-scale cytoskeletal reorganization. A prototypical example of cytoskeletal remodeling is mitotic spindle assembly, during which microtubules nucleate, undergo dynamic instability, bundle, and organize into a bipolar spindle. Key mechanisms of this process include regulated filament polymerization, crosslinking, and motor-protein activity. Remarkably, using passive crosslinkers, fission yeast can assemble a bipolar spindle in the absence of motor proteins.

Epigenetic modifications can extend over long genomic regions to form domain-level chromatin states that play critical roles in gene regulation. The molecular mechanism for the establishment and maintenance of these states is not fully understood and remains challenging to study with existing experimental techniques. Here we took a data-driven approach and parameterized an information-theoretic model to infer the formation mechanism of domain-level chromatin states from genome-wide epigenetic modification profiles.

A number of enzymes reportedly exhibit enhanced diffusion in the presence of their substrates, with a Michaelis-Menten-like concentration dependence. Although no definite explanation of this phenomenon has emerged, a physical picture of enzyme self-propulsion using energy from the catalyzed reaction has been widely considered. Here, we present a kinematic and thermodynamic analysis of enzyme self-propulsion that is independent of any specific propulsion mechanism. Using this theory, along with biophysical data compiled for all enzymes so far shown to undergo enhanced diffusion, we show that the propulsion speed required to generate experimental levels of enhanced diffusion exceeds the speeds of well-known active biomolecules, such as myosin, by several orders of magnitude.

Bacterial flagellar motor is one of the most complex and sophisticated nano machineries in nature. A duty ratio D is a fraction of time that the stator and the rotor interact and is a fundamental property to characterize the motor but remains to be determined. It is known that the stator units of the motor bind to and dissociate from the motor dynamically to control the motor torque depending on the load on the motor. At low load where the kinetics such as a proton translocation speed limits the rotation rate, the dependency of the rotation rate on the number of stator units N infers D; the dependency becomes larger for smaller D.

(Biophysical Journal 116, 1037–1048; March 19, 2019)

Contact guidance—the widely-known phenomenon of cell alignment induced by anisotropic environmental features—is an essential step in the organization of adherent cells, but the mechanisms by which cells achieve this orientational ordering remain unclear. Here we seeded myofibroblasts on substrates micropatterned with stripes of fibronectin and observed that contact guidance emerges at stripe widths much greater than the cell size. To understand the origins of this surprising observation, we combined morphometric analysis of cells and their subcellular components with a novel statistical framework for modelling non-thermal fluctuations of living cells.