You are currently viewing a new version of our website. To view the old version click .

Biophysica

Biophysica is an international, peer-reviewed, open access journal on applying the methods of physics, chemistry, and math to study biological systems, published quarterly online by MDPI.

Quartile Ranking JCR - Q4 (Biophysics)

All Articles (226)

Cytoskeletal Prestress Regulates RIG-I-Mediated Innate Immunity

  • Arpan Roy,
  • Sydney Sarver and
  • Jarod Beights
  • + 6 authors

Innate immunity is the body’s first line of defense for mounting robust antiviral signaling. However, the role of cytoskeletal prestress, a hallmark of cellular mechanotransduction, in regulating innate immune pathways such as retinoic acid-inducible gene I (RIG-I) signaling remains poorly understood. Herein, we show that cells on soft vs. rigid substrates elicit cytoskeletal prestress-dependent activation of RIG-I signaling, leading to differential type-I interferon (IFN) gene expression. Cells were cultured on soft (0.6 kPa) and stiff (8.5 kPa) substrates to modulate cellular traction and prestress, followed by transfection of Poly(I:C), a synthetic viral dsRNA mimic, to measure the RIG-I-mediated innate immune response. Cells on soft substrates show minimal activation of RIG-I signaling, resulting in low expression of IFN-β1 and other IFN-stimulated genes (ISGs), compared to cells on stiff substrates. We further demonstrate that activation of TANK Binding Kinase 1 (TBK1), a downstream effector of the RIG-I pathway, is inhibited in cells on soft substrates due to the cytoplasmic sequestration of the Yes-associated protein (YAP), a HIPPO pathway effector protein. In contrast, cells on stiffer substrates experienced decreased TBK1 inhibition due to the nuclear localization of YAP and exhibited elevated TBK1 activation and heightened IFN and ISG expressions. Together, we demonstrate that cytoskeletal prestress represents a key biophysical regulator of innate immune signaling.

1 November 2025

Cellular prestress regulates the innate immune response: (a) Phase images of HeLa cells seeded on 0.6 kPa and 8.5 kPa PA substrates. Quantification of (b) projected cell area (n = 20) shows that cells spread significantly more on 8.5 kPa substrates compared to 0.6 kPa, and (c) cell shape index (a measure of circularity; n = 20) indicates that cells on softer substrates adopt a more rounded morphology. (d–f) Basal RMS traction (n = 6) and prestress (n = 6) demonstrate that cells on stiffer substrates generate greater contractile forces. (g–j) Relative mRNA expression of key innate immune pathway genes following LMW-Poly(I:C) transfection on substrates of differing stiffness, measured from three independent experiments. Expression levels were normalized to the housekeeping gene Rps18. Scale bar, 20 μm.

Alzheimer’s disease is driven by multiple molecular drivers, including the pathological behavior of two intrinsically disordered proteins, amyloid-β (Aβ) and tau, whose aggregation is regulated by sequence-encoded ensembles and liquid–liquid phase separation (LLPS). This review integrates recent advances in biophysics, structural biology, and computational modeling to provide a multiscale perspective on how sequence determinants, post-translational modifications, and protein dynamics regulate the conformational landscapes of Aβ and tau. We discuss sequence-to-ensemble principles, from charge patterning and aromatic binders to familial mutations that reprogram structural ensembles and modulate LLPS. Structural studies, including NMR, SAXS, cryo-EM, and cryo-electron tomography, trace transitions from disordered monomers to fibrils and tissue-level structures. We highlight experimental challenges in LLPS assays, emerging standards for reproducibility, e.g., LLPSDB, PhaSePro, and FUS benchmarks, and computational strategies to refine and condensate modeling. Finally, we explore the therapeutic implications, including condensate-aware medicinal chemistry, ensemble-driven docking, and novel insights from clinical trials of anti-Aβ antibodies. Together, these perspectives underscore a paradigm shift toward environment- and ensemble-aware therapeutic design for Alzheimer’s and related protein condensation disorders.

7 November 2025

Distinct Thermal Response of SARS-CoV-2 Spike Proteins S1 and S2 by Coarse-Grained Simulations

  • Pornthep Sompornpisut,
  • Linh Truong Hoai and
  • Panisak Boonamnaj
  • + 2 authors

Large-scale computer simulations were employed to investigate the conformational response of the spike protein components S1 and S2 using a coarse-grained model. Temperature was systematically varied to assess the balance between stabilizing residue–residue interactions and thermal fluctuations. The resulting contact profiles reveal distinct segmental reorganization and self-assembly behaviors between S1 and S2. At lower, thermoresponsive temperatures, pronounced segmental globularization occurs in the N-terminal domain (NTD; M153–K202) and receptor-binding domain (RBD; E406–E471) of S1, whereas S2 exhibits alternating regions of high and low contact density. Increasing temperature reduces this segmental globularization, leaving only minor persistence at elevated temperatures. The temperature dependence of the radius of gyration (Rg) further demonstrates the contrasting thermal behaviors of S1 and S2. For S1, Rg increases continuously and monotonically with temperature, reaching a steady-state value approximately 50% higher than that at low temperature. In contrast, S2 displays a non-monotonic response: Rg initially rises to a maximum nearly sevenfold higher than its low-temperature value, then decreases with further temperature increase. Scaling analysis of the structure factor reveals that the globularity of S1 diminishes significantly upon heating, while S2 becomes modestly more compact yet retains its predominantly fibrous character.

31 October 2025

This study explored the use of physical methods, namely X-ray diffraction, atomic force microscopy, and energy-dispersive X-ray spectroscopy, to analyze the structure and composition of tear fluid desiccates. Tear samples were collected from patients with dry eye syndrome, glaucoma, and multiple sclerosis. Our results revealed significant differences in the crystallization patterns, chemical composition, and morphology of tear fluid among the disease groups compared to healthy individuals. XRD analysis identified variations in salt crystallization within tear fluid desiccates. AFM provided nanoscale morphological visualization. EDX determined the presence of key chemical elements. Our findings showed that changes in crystallization and unbalance of ionic composition in tear fluid may serve as potential markers for diagnosing ocular diseases. This study highlights the potential of these techniques for non-invasive diagnostics and contributes to the development of innovative strategies for monitoring structural properties in tear fluid desiccates of analyzed inflammatory, and neurodegenerative diseases.

25 October 2025

News & Conferences

Issues

Open for Submission

Editor's Choice

Get Alerted

Add your email address to receive forthcoming issues of this journal.

XFacebookLinkedIn
Biophysica - ISSN 2673-4125