European Biophysics Journal最新文献

Multiple myeloma is a blood cancer characterized by plasma cell proliferation and excessive production of monoclonal proteins, often leading to renal complications and other forms of organ damage. A set of nine immunoglobulin free light chain (FLC) samples purified from urine of multiple myeloma patients was subjected to sedimentation velocity analysis. Aim of the study was to track changes of the oligomerization state of each FLC while triggering reduction-induced aggregation into larger structures. Sedimentation velocity experiments, combined with further techniques sensitive to structural changes, were performed to determine the degree of FLC oligomerization in each patient sample under different experimental conditions. Structurally, the FLC monomers are stabilized by two intramolecular disulfide bonds, while covalent dimerization occurs through an unpaired C-terminal cysteine residue. Incubation with the reducing agent TCEP cleaves intra- and intermolecular disulfide bonds, destabilizing both monomers and dimers. Remarkably, different incubation times revealed that destabilized dimers do not dissociate into stable monomers but instead accumulate directly into oligomers and higher-order aggregates. In addition to larger aggregates, fragments with sizes around 1 S were detected with increasing TCEP incubation time. This fragmentation behavior was consistent among FLCs originating from the immunoglobulin kappa variable 1-33 gene (IGKV1-33). Sedimentation velocity-based characterization of FLCs can provide insights into the relationship between their stability and aggregation capacity. An understanding of this relationship is crucial for the development of therapeutic strategies to prevent renal complications associated with monoclonal gammopathies such as multiple myeloma.

Individual cell growth can be affected by the presence of adjacent cells through a complex and multi-factorial biological process known alternatively as contact inhibition or confluence sensing. In a previous paper (Hall D (2024) Equations describing semi-confluent cell growth (I) Analytical approximations. Biophys Chem 307:107173), sets of differential equations (with implicit analytical solutions) were developed to describe completely symmetrical cases of multicellular colony growth affected by variable levels of contact inhibition. Here we develop a model based on a spherical cap approximation of colony growth, that is able to describe variable contact inhibition for non-symmetrical multilayer cell formation on a solid plate. Although the model is realized as a set of interrelated ordinary differential equations, it is effectively governed by two parameters and is therefore capable for use in quantitative analysis of the kinetics of cell culture parameters such as shape, colony size and receding contact angle. The model is capable of accounting for transitions from monolayer to multilayer growth in a robust fashion.

A foundational understanding of biophysics and fluid dynamics is critical for comprehending cardiovascular physiological phenomena, yet medical students often struggle with the mathematical complexity. Traditional teaching methods, including in vivo and in vitro experiments, are increasingly being replaced due to ethical concerns, leading to the adoption of in silico models. This study developed a biophysical model simulating the vascular tree using pumps and silicone vessels. Central to the model is a silicone aorta with pressure sensors, immersed in water, and connected to rubber and peristaltic pumps to generate pulse waves. Transparent silicone tubes, decreasing in diameter, mimic the vascular system, while one-way valves regulate flow. Pressure was measured via sensors at key points, with data digitized and visualized in real-time. A 40% ethyl alcohol solution, mimicking blood viscosity, was used. The exercise aimed to teach wave propagation, pressure waveform analysis, pulse wave velocity calculation, and the effects of resistance on wave propagation. Pulse wave propagation was demonstrated with manual compression of the rubber pump generating the input signal. Time delays between pressure waveforms at different sensors were used to calculate pulse wave velocity. Wave reflections were observed as the forward wave traveled to the aortic bifurcation, reflected backward, and then reflected again upon reaching a valve. Reflections were further analyzed with constrictions and added resistance in the system, with careful observation needed to discern the superimposed waves.

The tumor suppressor p53, extensively studied for over 40 years, is a key regulator of various cellular pathways, often functioning independently of its transcriptional activity. Notably, p53 has been shown to play a crucial role in DNA repair, not only in sensing DNA damage but also in influencing repair pathway choice. This work assesses the influence of p53 on the recruitment and activity of the NHEJ mediator 53BP1, focusing specifically on common p53 hotspot mutations found in human cancers. The aim is to understand how these mutations impair DNA damage response mechanisms and contribute to genetic instability, which enhances tumor survival. Analysis of p53 missense mutations (R248W, R273C, G245S) revealed mutation-specific effects on 53BP1 and RIF1 recruitment, with G245S retaining wild-type-like 53BP1 recruitment but still exhibiting enhanced BRCA1 foci formation. Given the widespread activation of NHEJ throughout the cell cycle, especially in response to radiotherapy and chemotherapy, gaining insight into how p53 mutations affect this response is vital for developing future therapeutic strategies.

The study of bacteria swimming behavior or their interaction with other bacteria or cells requires an efficient and flexible tool for bacteria manipulation. Optical tweezers have been shown to be perfectly adapted for this task. Here we report optical trapping of pathogen Pseudomonas aeruginosa bacteria using optical fiber tweezers with dedicated nanostructured optical fibers. Well-aligned straight chains of up to ten bacteria were observed with optical fiber tips, whereas contactless trapping was realized at distances of 100 and 45 µm for Fresnel lens fibers and TIROFs, respectively. Very efficient trapping at laser powers as low as 3.7 mW was achieved. The bacteria vitality is an important parameter in trapping experiments. Mean square displacement and speed autocorrelation methods were applied to obtain a vitality measure and to classify the free bacteria trajectories into free floating, running, and run-wrap-run categories. The high frame rates of our observation videos allow us to reveal a relation between bacteria speed and bacteria orientation oscillations.