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Eukaryotic genomes self-organize into diverse three-dimensional (3D) chromatin conformations through intranuclear long-range interactions, yet it remains challenging to interpret how concurrent interactions combine along a chromatin polymer to shape measurable conformational readouts. Building on a minimal harmonic polymer model and the Gaussian covariance formalism, we present a 3D genome circuit representation that reorganizes the covariance-derived effective interaction strength (EIS) of a target locus pair into motif-level interaction patterns.

Muscle contraction is a prototypical multiscale chemomechanical process in which ATP hydrolysis at the molecular level drives force generation and mechanical work at larger scales. A central challenge is to incorporate the free energy supplied by ATP hydrolysis into a mechanical cross-bridge model in a way that is thermodynamically consistent and connects microscopic motor cycling to macroscopic force generation. Here we use the Energetic Variational Approach (EnVarA) to combine Hill’s cycle-affinity viewpoint with Huxley’s sliding-filament mechanics in a single thermodynamically consistent framework.

Accurately predicting RNA secondary structure remains a central challenge in computational biology. Although standard methods based on minimum free energy (MFE) optimization often produce good predictions, their accuracy varies, and they can still miss helices present in known structures. Because the thermodynamics of multibranch loops strongly influence these predictions, we examine how changes to the multiloop initiation and branching penalties affect prediction performance, focusing specifically on recall.

Biomolecular condensates formed by phase separation inside cells often exhibit viscoelastic behavior, yet their shape recovery and fusion dynamics are frequently interpreted using purely viscous models. Here, we develop a unified theoretical and computational framework to quantify how viscoelasticity governs these two fundamental processes. We combine analytical theory for small-deformation shape recovery with axisymmetric finite-element simulations based on the Oldroyd-B constitutive model to systematically investigate both shape recovery and droplet fusion under comparable physical conditions.

The interactions among condensate-forming biomolecules dictate both the specificity and properties of these condensates, including their fluid-like nature and material exchange dynamics among condensate droplets. While interaction specificity is typically associated with mean interaction lifetimes, the role of interaction lifetime distributions in shaping condensate behavior remains unexplored. This is a critical gap where extensive research has focused on interaction strengths and mean lifetimes.

This special issue of Biophysical Journal is in memoriam of Martin Karplus, a pioneer of computational molecular biophysics and Nobel laureate in chemistry, who passed away in December 2024. The response to the announcement of the special issue was enthusiastic, and we are thrilled to count 34 articles covering a staggering number of biological subjects. With a special note to all the authors, we also express our gratitude to our co-editors, Andrej Sali, Monte Pettitt, Tamar Schlick, and John Kuriyan, for putting together the issue.

In eukaryotic cell chemotaxis, many cells extend and retract transient actin-driven protrusions at their membrane that facilitate both the detection of external chemical gradients and directional movement via cell–matrix coupling and traction. Although extensive experimental work has detailed how cellular protrusions and morphology vary under different environmental conditions, the mechanistic principles linking protrusive activity to these factors remain poorly understood. Here, we model the extension of actin-based protrusions in chemotaxis as an optimisation problem, wherein cells balance the detection of chemical gradients with the energetic cost of protrusion formation.

Fibrils formed by 40- and 42-residue amyloid-β peptides (Aβ40 and Aβ42) are polymorphic, containing molecular structures that vary with growth conditions in ways that are not fully understood. Here we use cryogenic electron microscopy to characterize the structure of rapidly twisting Aβ40 fibrils, for which the distance between apparent width minima in electron microscope images (“cross-over distances”) is approximately 25 nm. From samples grown under a single set of growth conditions, we obtain high-resolution structures for three different rapidly twisting polymorphs.

Pulmonary surfactant adsorbs rapidly to the surface of the liquid layer that lines the alveolar air-sacks of the lungs. When compressed by the decreasing alveolar surface area during exhalation, the adsorbed films avoid collapse from the air/liquid interface and reduce surface tension to exceptionally low levels. Results with factors ωηιχη induce surfactant lipids to increase intrinsic curvature suggest that adsorption proceeds via a curved rate-limiting structure. Samples with negative intrinsic curvature, with a concave hydrophilic surface, adsorb rapidly, but they also desorb quickly.

(Biophysical Journal 125, 1–15; June 16, 2026)

Interactions between cytosolic biomolecules and the bacterial inner membrane are fundamental to many cellular processes, yet directly measuring their binding kinetics in living cells remains challenging. Conventional two-dimensional single-molecule tracking analyses can be insufficient, particularly when membrane association does not markedly alter the diffusion rate. Here, we present a method to recover membrane interaction kinetics from three-dimensional single-molecule trajectories in rod-shaped bacteria.

Actin filaments created by the Arp2/3 complex form branched networks that grow and push against cellular membranes. We employ theory and simulation to describe how membrane surfaces accelerate filament assembly via clustering of proteins, including WAVE-family nucleation promoting factors, that bind actin monomers and/or profilin-actin complexes. Briefly, thermal fluctuations drive filament tips on constrained, two-dimensional random walks across the membrane, where they collide with actin-charged polymerases.