Mikko Karttunen

Soft cancer cells embedded in stiffer epithelial layers migrate in bursts, which prior simulations have attributed to their deformability. In a dense layer, however, interfacial tension sets two things at once: the energy cost of a deformation and the rate at which it relaxes. Here we disentangle the two in an active phase-field model of a near-confluent monolayer in which relaxation rate and free energy can be varied independently. Crowding slows cells not by pushing them back bodily but through the relaxation of their own deformations against neighbours, which cancels most of their propulsion. Slowing this relaxation in a minority of cells, at unchanged energetics and propulsion, more than doubles their transport and speeds up the untouched majority by half. Conversely, the advantage of soft cells vanishes, and at high soft-cell fractions reverses, once their relaxation is made as fast as that of normal cells. Independent of composition, mixtures transport like a uniform layer with the geometric-mean interfacial tension. Passive relaxation kinetics thus emerges as an independent lever on transport, suggesting that the fluidity of heterogeneous tissues may depend on how quickly cells recover their shape, not only on how stiff they are.

Polymeric micelles are widely studied drug delivery platforms whose interactions with plasma proteins influence in vivo performance. However, the combined effects of non-pEG hydrophilic coronas and high drug loading on protein adsorption remain poorly understood. We performed all-atom molecular dynamics (MD) simulations to investigate the association of three plasma proteins: apolipoprotein E (ApoE), human serum albumin (HSA), and immunoglobulin G (IgG), with curcumin-loaded ABA triblock copolymer micelles. To isolate corona effects, micelles shared an hydrophobic core chemistry and differed only in the hydrophilic A-block: poly(ethylene glycol) (pEG), poly(N,N-dimethylacrylamide) (pDMAA), or poly(sarcosine) (pSAR). Two drug loadings (20% and 60% drug/polymer mass ratio) were examined. Binding was assessed via contact areas, hydrogen bonds, and interaction energies. pEG micelles showed the strongest protein association. pDMAA and pSAR exhibited weaker, surface-limited interactions. These simulations provide molecular-level insight into protein adsorption on drug-loaded polymeric micelles and compare alternative hydrophilic A-blocks to pEG.

Reactive oxygen species generated during inflammation can oxidize viral envelope lipids, with outcomes ranging from modulated infectivity to viral inactivation.

Polymeric micelles are established delivery platforms for hydrophobic drugs. The molecular interactions governing their structure and function remain, however, poorly understood. All‐atom molecular dynamics simulations are used to investigate drug‐loaded ABA‐type triblock copolymer micelles with a hydrophobic poly(2‐ n ‐butyl‐2‐oxazine) core and hydrophilic coronas composed of poly(ethylene glycol) (pEG), poly( N , N ‐dimethylacrylamide) (pDMAA), and poly(sarcosine) (pSAR). Here, pDMAA and pSAR are considered as alternative polymers to address emerging pEG immunogenicity. Three micellar formulations are examined at moderate (20%) and high (60%) loadings of curcumin as a model hydrophobic drug. The simulations reveal that pEG‐based micelles exhibit higher hydration and looser corona structures compared to pDMAA and pSAR micelles. In pEG micelles, curcumin localizes primarily within the hydrophobic core, whereas in pDMAA and pSAR micelles it is more uniformly distributed. At both drug loadings, curcumin preferentially aggregates into a single stable cluster, not densely packed, and interpenetrated by polymer chains. Micelles with pDMAA and pSAR coronas exhibit enhanced stability, reflecting higher internal density and tighter curcumin packing. Hydrogen bond analysis reveals the strongest curcumin‐hydrophilic A‐block interactions in pDMAA micelles, moderate loading‐dependent interactions in pSAR micelles, and minimal hydrogen‐bonding in pEG micelles due to corona hydration.

Atomic substitution provides a controlled route to engineer lattice dynamics in low-symmetry two-dimensional materials. Here, by combining polarization-resolved Raman spectroscopy and first-principles calculations, we investigate the evolution of phonon characteristics in CrSBr 1 − x Cl x ( 0 ⩽ x ⩽ ∼ 0.5 ) upon partial substitution of Br with Cl atoms. Progressive Cl substitution of Br induces systematic shifts of parent CrSBr out-of-plane A g phonon modes and activates additional Raman features. These features persist across different polarization configurations and excitation energies, reflecting substitution-induced symmetry lowering and local lattice perturbations. Explicit supercell phonon calculations combined with Raman Γ -density-of-states simulations identify these features as symmetry-lowered descendants of parent modes arising from alloy disorder. Complementary strain-dependent calculations reveal that anisotropic lattice compression plays a key role in renormalizing Cr–S dominated phonons. Under near-resonant excitation, stimulated Raman scattering-like amplification remains observable with increasing Cl content, highlighting the resilience of anisotropic electron–phonon coupling in this system.

In this study, we used all-atom molecular dynamics (MD) simulations to investigate the behavior of poly­( l -lactic acid) (PLLA) in the presence of 0, 1, 2, 6, and 12 m-% water. We focus on understanding how the contacts between various atoms of adjacent PLLA chains evolve and how these changes influence the system’s volume, density, and mechanical and thermodynamic properties. We observe that as the solvent concentration increases, the number of contacts between the atoms of the adjacent PLLA chains decreases, leading to swelling when water penetrates between the polymer chains. However, a small amount of water is seen to facilitate contacts between the oxygen and hydrogen atoms, and the volume of the system contracts. This variation in interchain contacts correlates with changes in density. The contraction is also reflected in the thermal expansion coefficient, which decreases slightly at 1–2 m-%, but then increases at higher water contents due to swelling. In addition, the isothermal compressibility decreases and the isothermal bulk modulus increases; in other words, the resistance to compression increases as 2–6 m-% water is added. Moreover, the specific heat capacity increases after 6 m-%, by 11% at 12 m-%. Our simulation results show strong agreement with the experimental observations. The insights gained from this study improve our understanding of the molecular interactions between PLLA chains and the mechanistic degradation steps favored in the presence of water. These findings have significant implications for the design of sustainable and biodegradable materials, with applications ranging from food packaging to medical uses.

Capsaicin is a natural bioactive compound found in chili peppers, with promising potential in various pharmacological applications, including analgesic, antipruritic, anti-inflammatory, anticancer, and antioxidant effects. Its clinical use, however, remains limited due to poor bioavailability, low aqueous solubility, and limited stability. To address these challenges, loading capsaicin in a small liposome bilayer has been proposed to enhance its transport across biological membranes. In this work, we perform molecular dynamics (MD) simulations to study the behavior of capsaicin in lipid bilayers. Two lipid types, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1,2-dipalmitoyl-rac-glycero-3-phosphocholine (DPPC), are used to investigate the effects of unsaturation in the lipid tails. Simulations were conducted under two initial conditions: (1) capsaicin molecules placed in the aqueous phase to study permeation behavior and (2) capsaicin preinserted into the bilayer to assess its equilibrium positioning and to study its behavior in the membrane environment. Our results show that capsaicin tends to aggregate in water with only small aggregates capable of passive permeation into the membrane. The POPC bilayer exhibits a greater capsaicin uptake than the DPPC bilayer, which is attributed to its larger area per lipid. Mass-density profiles indicate the preferred localization of capsaicin within the bilayers, which is consistent with the minimum free energy observed in the potential of mean force (PMF) profiles for translocated molecules into the bilayer. Notably, capsaicin does not significantly change the bilayer thickness and area per lipid when the bilayer is in the liquid phase. It decreases the lipid area per lipid, while maintaining a stable area per capsaicin. The estimated area per capsaicin molecule within the bilayer is 0.415 ± 0.010 nm². Interestingly, when the bilayer was in the gel phase, the ordered lipid was disrupted by the capsaicin. These findings provide valuable insights into the membrane interactions of capsaicin and support the rational design of liposomal delivery systems to enhance its pharmaceutical potential.

Cell-penetrating peptides (CPPs) are relatively short, charged, or amphipathic peptides that facilitate the translocation of cargo across cellular membranes. One such peptide is penetratin, a 16-amino-acid cationic CPP. It exhibits minimal interaction with zwitterionic lipid bilayers but strongly interacts with anionic membranes. We investigated the interactions of unmodified penetratin (Pen1) and its capped analogue (Pen2) using a combination of spectroscopic, calorimetric, tensiometric, and molecular dynamics (MD) approaches with models of bacterial (anionic) and human cell membranes. Both Pen variants have a +7 charge; Pen2 shows greater structural stability, enhanced helical propensity, and deeper membrane insertion (as evidenced by circular dichroism and fluorescence spectroscopy, and surface pressure measurements). In bacterial membranes, Pen1 binds exothermically, while Pen2 exhibits a two-stage process: an initial entropy-driven endothermic binding followed by exothermic interaction. End-group capping promotes more stable and compact peptide conformations, facilitates water shedding, and increases membrane hydrogen bonding.

Reactive oxygen species generated during inflammation can oxidize viral envelope lipids, with outcomes ranging from modulated infectivity to viral inactivation. For SARS-CoV-2, the molecular mechanisms by which membrane lipid oxidation influences spike protein anchoring remain poorly understood. We use all-atom molecular dynamics (MD) simulations to quantify how graded oxidation of 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphocholine (POPC) affects the anchoring of the SARS-CoV-2 spike transmembrane (TM) region in an endoplasmic-reticulum–Golgi intermediate compartment (ERGIC)-like multicomponent membrane. Viral envelopes containing 0, 25, 50, 75, and 100% oxidized POPC (PoxnoPC) corresponding to 0 − 55% oxidation of all PO-type phospholipids were simulated with the spike TM helix and cytoplasmic tail embedded in a POPC/POPE/POPI/POPS/cholesterol mixture. Steered MD and umbrella sampling were used to calculate the potential of mean force (PMF) for extracting the TM+CT region along the membrane normal. Partial oxidation (25 − 75% POPC) produced reductions in the detachment barrier that were not statistically distinguishable from the native system within the sampling uncertainty, whereas full POPC oxidation lowered the anchoring free energy by about 23% (from 606 ± 39 to 464 ± 38 kJ mol ⁻¹ ), indicating that oxidation of roughly half of the glycerophospholipids can measurably weaken spike-membrane coupling. Despite this reduction, the remaining barrier (about 180 k _B T ) is still large, suggesting that oxidation alone may be insufficient for spontaneous spike detachment and likely acts synergistically with mechanical forces during fusion or immune engagement. Analysis of acyl-chain order parameters, area per lipid, membrane thickness, number-density profiles, and lateral lipid clustering reveals that POPC peroxidation decreases lipid order, thins and softens the bilayer, and disrupts cholesterol-stabilized clusters that refer to large cooperative lipid assemblies (>10 lipids) identified via RDF-based clustering. These oxidation-induced changes reduce hydrophobic matching around the TM helix and facilitate its extraction from the viral envelope. Our results provide a mechanistic link between lipid peroxidation, membrane nanostructure, and spike anchoring, supporting lipid oxidation for example during cold atmospheric plasma or ozone treatment as a physically grounded contributing antiviral mechanism against SARS-CoV-2.