Dynamin 1xA interacts with Endophilin A1 via its spliced long C-terminus for ultrafast endocytosis.

Dynamin 1 mediates fission of endocytic synaptic vesicles in the brain and has two major splice variants, Dyn1xA and Dyn1xB, which are nearly identical apart from the extended C-terminal region of Dyn1xA. Despite a similar set of binding partners, only Dyn1xA is enriched at endocytic zones and accelerates vesicle fission during ultrafast endocytosis. Here, we report that Dyn1xA achieves this localization by preferentially binding to Endophilin A1 through a newly defined binding site within its long C-terminal tail extension. Endophilin A1 binds this site at higher affinity than the previously reported site, and the affinity is determined by amino acids within the Dyn1xA tail but outside the binding site. This interaction is regulated by the phosphorylation state of two serine residues specific to the Dyn1xA variant. Dyn1xA and Endophilin A1 colocalize in patches near the active zone, and mutations disrupting Endophilin A binding to the long tail cause Dyn1xA mislocalization and stalled endocytic pits on the plasma membrane during ultrafast endocytosis. Together, these data suggest that the specificity for ultrafast endocytosis is defined by the phosphorylation-regulated interaction of Endophilin A1 with the C-terminal extension of Dyn1xA.

Unraveling dynamic protein structures by two-dimensional infrared spectra with a pretrained machine learning model.

Dynamic protein structures are crucial for deciphering their diverse biological functions. Two-dimensional infrared (2DIR) spectroscopy stands as an ideal tool for tracing rapid conformational evolutions in proteins. However, linking spectral characteristics to dynamic structures poses a formidable challenge. Here, we present a pretrained machine learning model based on 2DIR spectra analysis. This model has learned signal features from approximately 204,300 spectra to establish a "spectrum-structure" correlation, thereby tracing the dynamic conformations of proteins. It excels in accurately predicting the dynamic content changes of various secondary structures and demonstrates universal transferability on real folding trajectories spanning timescales from microseconds to milliseconds. Beyond exceptional predictive performance, the model offers attention-based spectral explanations of dynamic conformational changes. Our 2DIR-based pretrained model is anticipated to provide unique insights into the dynamic structural information of proteins in their native environments.

Imaging hot photocarrier transfer across a semiconductor heterojunction with ultrafast electron microscopy.

Semiconductor heterojunctions have gained significant attention for efficient optoelectronic devices owing to their unique interfaces and synergistic effects. Interaction between charge carriers with the heterojunction plays a crucial role in determining device performance, while its spatial-temporal mapping remains lacking. In this study, we employ scanning ultrafast electron microscopy (SUEM), an emerging technique that combines high spatial-temporal resolution and surface sensitivity, to investigate photocarrier dynamics across a Si/Ge heterojunction. Charge dynamics are selectively examined across the junction and compared to far bulk areas, through which the impact of the built-in potential, band offsets, and surface effects is directly visualized. In particular, we find that the heterojunction drastically modifies the hot photocarrier diffusivities in both Si and Ge regions due to charge trapping. These findings are further elucidated with insights from the band structure and surface potential measured by complementary techniques. This work demonstrates the tremendous effect of heterointerfaces on hot photocarrier dynamics and showcases the potential of SUEM in characterizing realistic optoelectronic devices.

Ultrafast transient absorption spectra and kinetics of human blue cone visual pigment at room temperature.

The ultrafast photochemical reaction mechanism, transient spectra, and transition kinetics of the human blue cone visual pigment have been recorded at room temperature. Ultrafast time-resolved absorption spectroscopy revealed the progressive formation and decay of several metastable photo-intermediates, corresponding to the Batho to Meta-II photo-intermediates previously observed with bovine rhodopsin and human green cone opsin, on the picosecond to millisecond timescales following pulsed excitation. The experimental data reveal several interesting similarities and differences between the photobleaching sequences of bovine rhodopsin, human green cone opsin, and human blue cone opsin. While Meta-II formation kinetics are comparable between bovine rhodopsin and blue cone opsin, the transition kinetics of earlier photo-intermediates and qualitative characteristics of the Meta-I to Meta-II transition are more similar for blue cone opsin and green cone opsin. Additionally, the blue cone photo-intermediate spectra exhibit a high degree of overlap with uniquely small spectral shifts. The observed variation in Meta-II formation kinetics between rod and cone visual pigments is explained based on key structural differences.

Ultrafast universal fabrication of configurable porous silicone-based elastomers by Joule heating chemistry.

Silicone-based elastomers (SEs) have been extensively applied in numerous cutting-edge areas, including flexible electronics, biomedicine, 5G smart devices, mechanics, optics, soft robotics, etc. However, traditional strategies for the synthesis of polymer elastomers, such as bulk polymerization, suspension polymerization, solution polymerization, and emulsion polymerization, are inevitably restricted by long-time usage, organic solvent additives, high energy consumption, and environmental pollution. Here, we propose a Joule heating chemistry method for ultrafast universal fabrication of SEs with configurable porous structures and tunable components (e.g., graphene, Ag, graphene oxide, TiO2, ZnO, Fe3O4, V2O5, MoS2, BN, g-C3N4, BaCO3, CuI, BaTiO3, polyvinylidene fluoride, cellulose, styrene-butadiene rubber, montmorillonite, and EuDySrAlSiOx) within seconds by only employing H2O as the solvent. The intrinsic dynamics of the in situ polymerization and porosity creation of these SEs have been widely investigated. Notably, a flexible capacitive sensor made from as-fabricated silicone-based elastomers exhibits a wide pressure range, fast responses, long-term durability, extreme operating temperatures, and outstanding applicability in various media, and a wireless human-machine interaction system used for rescue activities in extreme conditions is established, which paves the way for more polymer-based material synthesis and wider applications.

Ultrafast terahertz Stark spectroscopy reveals the excited-state dipole moments of retinal in bacteriorhodopsin.

The photoinduced all-trans to 13-cis isomerization of the retinal Schiff base represents the ultrafast first step in the reaction cycle of bacteriorhodopsin (BR). Extensive experimental and theoretical work has addressed excited-state dynamics and isomerization via a conical intersection with the ground state. In conflicting molecular pictures, the excited state potential energy surface has been modeled as a pure S[Formula: see text] state that intersects with the ground state, or in a 3-state picture involving the S[Formula: see text] and S[Formula: see text] states. Here, the photoexcited system passes two crossing regions to return to the ground state. The electric dipole moment of the Schiff base in the S[Formula: see text] and S[Formula: see text] state differs strongly and, thus, its measurement allows for assessing the character of the excited-state potential. We apply the method of ultrafast terahertz (THz) Stark spectroscopy to measure electric dipole changes of wild-type BR and a BR D85T mutant upon electronic excitation. A fully reversible transient broadening and spectral shift of electronic absorption is induced by a picosecond THz field of several megavolts/cm and mapped by a 120-fs optical probe pulse. For both BR variants, we derive a moderate electric dipole change of 5 [Formula: see text] 1 Debye, which is markedly smaller than predicted for a neat S[Formula: see text]-character of the excited state. In contrast, S[Formula: see text]-admixture and temporal averaging of excited-state dynamics over the probe pulse duration gives a dipole change in line with experiment. Our results support a picture of electronic and nuclear dynamics governed by the interaction of S[Formula: see text] and S[Formula: see text] states in a 3-state model.

Ultrafast generation of hidden phases via energy-tuned electronic photoexcitation in magnetite.

Phase transitions occurring in nonequilibrium conditions can evolve through high-energy intermediate states inaccessible via equilibrium adiabatic conditions. Because of the subtle nature of such hidden phases, their direct observation is extremely challenging and requires simultaneous visualization of matter at subpicoseconds and subpicometer scales. Here, we show that a magnetite crystal in the vicinity of its metal-to-insulator transition evolves through different hidden states when controlled via energy-tuned ultrashort laser pulses. By directly monitoring magnetite's crystal structure with ultrafast electron diffraction, we found that upon near-infrared (800 nm) excitation, the trimeron charge/orbital ordering pattern is destroyed in favor of a phase-separated state made of cubic-metallic and monoclinic-insulating regions. On the contrary, visible light (400 nm) activates a photodoping charge transfer process that further promotes the long-range order of the trimerons by stabilizing the charge density wave fluctuations, leading to the reinforcement of the monoclinic insulating phase. Our results demonstrate that magnetite's structure can evolve through completely different metastable hidden phases that can be reached long after the initial excitation has relaxed, breaking ground for a protocol to control emergent properties of matter.

Chemical bond reorganization in intramolecular proton transfer revealed by ultrafast X-ray photoelectron spectroscopy.

Time-resolved X-ray photoelectron spectroscopy (TR-XPS) is used in a simulation study to monitor the excited state intramolecular proton transfer between oxygen and nitrogen atoms in 2-(iminomethyl)phenol. Real-time monitoring of the chemical bond breaking and forming processes is obtained through the time evolution of excited-state chemical shifts. By employing individual atomic probes of the proton donor and acceptor atoms, we predict distinct signals with opposite chemical shifts of the donor and acceptor groups during proton transfer. Details of the ultrafast bond breaking and forming dynamics are revealed by extending the classical electron spectroscopy chemical analysis to real time. Through a comparison with simulated time-resolved photoelectron spectroscopy at the valence level, the distinct advantage of TR-XPS is demonstrated thanks to its atom specificity.

PanDepth, an ultrafast and efficient genomic tool for coverage calculation.

Coverage quantification is required in many sequencing datasets within the field of genomics research. However, most existing tools fail to provide comprehensive statistical results and exhibit limited performance gains from multithreading. Here, we present PanDepth, an ultra-fast and efficient tool for calculating coverage and depth from sequencing alignments. PanDepth outperforms other tools in computation time and memory efficiency for both BAM and CRAM-format alignment files from sequencing data, regardless of read length. It employs chromosome parallel computation and optimized data structures, resulting in ultrafast computation speeds and memory efficiency. It accepts sorted or unsorted BAM and CRAM-format alignment files as well as GTF, GFF and BED-formatted interval files or a specific window size. When provided with a reference genome sequence and the option to enable GC content calculation, PanDepth includes GC content statistics, enhancing the accuracy and reliability of copy number variation analysis. Overall, PanDepth is a powerful tool that accelerates scientific discovery in genomics research.

SPDesign: protein sequence designer based on structural sequence profile using ultrafast shape recognition.

Protein sequence design can provide valuable insights into biopharmaceuticals and disease treatments. Currently, most protein sequence design methods based on deep learning focus on network architecture optimization, while ignoring protein-specific physicochemical features. Inspired by the successful application of structure templates and pre-trained models in the protein structure prediction, we explored whether the representation of structural sequence profile can be used for protein sequence design. In this work, we propose SPDesign, a method for protein sequence design based on structural sequence profile using ultrafast shape recognition. Given an input backbone structure, SPDesign utilizes ultrafast shape recognition vectors to accelerate the search for similar protein structures in our in-house PAcluster80 structure database and then extracts the sequence profile through structure alignment. Combined with structural pre-trained knowledge and geometric features, they are further fed into an enhanced graph neural network for sequence prediction. The results show that SPDesign significantly outperforms the state-of-the-art methods, such as ProteinMPNN, Pifold and LM-Design, leading to 21.89%, 15.54% and 11.4% accuracy gains in sequence recovery rate on CATH 4.2 benchmark, respectively. Encouraging results also have been achieved on orphan and de novo (designed) benchmarks with few homologous sequences. Furthermore, analysis conducted by the PDBench tool suggests that SPDesign performs well in subdivided structures. More interestingly, we found that SPDesign can well reconstruct the sequences of some proteins that have similar structures but different sequences. Finally, the structural modeling verification experiment indicates that the sequences designed by SPDesign can fold into the native structures more accurately.

Topological damping in an ultrafast giant cell.

Cellular systems are known to exhibit some of the fastest movements in biology, but little is known as to how single cells can dissipate this energy rapidly and adapt to such large accelerations without disrupting internal architecture. To address this, we investigate Spirostomum ambiguum-a giant cell (1-4 mm in length) well-known to exhibit ultrafast contractions (50% of body length) within 5 ms with a peak acceleration of 15[Formula: see text]. Utilizing transmitted electron microscopy and confocal imaging, we identify an association of rough endoplasmic reticulum (RER) and vacuoles throughout the cell-forming a contiguous fenestrated membrane architecture that topologically entangles these two organelles. A nearly uniform interorganelle spacing of 60 nm is observed between RER and vacuoles, closely packing the entire cell. Inspired by the entangled organelle structure, we study the mechanical properties of entangled deformable particles using a vertex-based model, with all simulation parameters matching 10 dimensionless numbers to ensure dynamic similarity. We demonstrate how entangled deformable particles respond to external loads by an increased viscosity against squeezing and help preserve spatial relationships. Because this enhanced damping arises from the entanglement of two networks incurring a strain-induced jamming transition at subcritical volume fractions, which is demonstrated through the spatial correlation of velocity direction, we term this phenomenon "topological damping." Our findings suggest a mechanical role of RER-vacuolar meshwork as a metamaterial capable of damping an ultrafast contraction event.

Ultrafast electron localization and screening in a transition metal dichalcogenide.

The coupling of light to electrical charge carriers in semiconductors is the foundation of many technological applications. Attosecond transient absorption spectroscopy measures simultaneously how excited electrons and the vacancies they leave behind dynamically react to the applied optical fields. In compound semiconductors, these dynamics can be probed via any of their atomic constituents with core-level transitions into valence and conduction band. Typically, the atomic species forming the compound contribute comparably to the relevant electronic properties of the material. One therefore expects to observe similar dynamics, irrespective of the choice of atomic species via which it is probed. Here, we show in the two-dimensional transition metal dichalcogenide semiconductor MoSe2, that through a selenium-based core-level transition we observe charge carriers acting independently from each other, while when probed through molybdenum, the collective, many-body motion of the carriers dominates. Such unexpectedly contrasting behavior can be explained by a strong localization of electrons around molybdenum atoms following absorption of light, which modifies the local fields acting on the carriers. We show that similar behavior in elemental titanium metal [M. Volkov et al., Nat. Phys. 15, 1145-1149 (2019)] carries over to transition metal-containing compounds and is expected to play an essential role for a wide range of such materials. Knowledge of independent particle and collective response is essential for fully understanding these materials.

Direct observation of the collective modes of the charge density wave in the kagome metal CsV3Sb5.

A recently discovered group of kagome metals AV[Formula: see text]Sb[Formula: see text] (A = K, Rb, Cs) exhibit a variety of intertwined unconventional electronic phases, which emerge from a puzzling charge density wave phase. Understanding of this charge-ordered parent phase is crucial for deciphering the entire phase diagram. However, the mechanism of the charge density wave is still controversial, and its primary source of fluctuations-the collective modes-has not been experimentally observed. Here, we use ultrashort laser pulses to melt the charge order in CsV[Formula: see text]Sb[Formula: see text] and record the resulting dynamics using femtosecond angle-resolved photoemission. We resolve the melting time of the charge order and directly observe its amplitude mode, imposing a fundamental limit for the fastest possible lattice rearrangement time. These observations together with ab initio calculations provide clear evidence for a structural rather than electronic mechanism of the charge density wave. Our findings pave the way for a better understanding of the unconventional phases hosted on the kagome lattice.

Coherent detection of hidden spin-lattice coupling in a van der Waals antiferromagnet.

Strong interactions between different degrees of freedom lead to exotic phases of matter with complex order parameters and emergent collective excitations. Conventional techniques, such as scattering and transport, probe the amplitudes of these excitations, but they are typically insensitive to phase. Therefore, novel methods with phase sensitivity are required to understand ground states with phase modulations and interactions that couple to the phase of collective modes. Here, by performing phase-resolved coherent phonon spectroscopy (CPS), we reveal a hidden spin-lattice coupling in a vdW antiferromagnet FePS3 that eluded other phase-insensitive conventional probes, such as Raman and X-ray scattering. With comparative analysis and analytical calculations, we directly show that the magnetic order in FePS3 selectively couples to the trigonal distortions through partially filled t2g orbitals. This magnetoelastic coupling is linear in magnetic order and lattice parameters, rendering these distortions inaccessible to inelastic scattering techniques. Our results not only capture the elusive spin-lattice coupling in FePS3 but also establish phase-resolved CPS as a tool to investigate hidden interactions.

Ultrafast nonequilibrium dynamics of rotons in superfluid helium.

Short-time dynamics of superfluids far from equilibrium remains largely unknown, despite its importance for key processes in these systems. Here, we describe a method for locally perturbing the density of superfluid helium via the excitation of roton pairs with ultrashort laser pulses. By measuring the time dependence of this perturbation, we track the nonequilibrium dynamics of the two-roton states on femtosecond and picosecond timescales. Our results reveal an ultrafast equilibration of roton pairs as they thermalize with the colder equilibrium quasiparticle gas. Future applications of this technique to different temperature and pressure regimes, in various superfluids, will enable to probe rapid nucleation and decay processes, as well as metastable Bose-Einstein condensates of rotons and roton pairs.

Elucidating interprotein energy transfer dynamics within the antenna network from purple bacteria.

In photosynthesis, absorbed light energy transfers through a network of antenna proteins with near-unity quantum efficiency to reach the reaction center, which initiates the downstream biochemical reactions. While the energy transfer dynamics within individual antenna proteins have been extensively studied over the past decades, the dynamics between the proteins are poorly understood due to the heterogeneous organization of the network. Previously reported timescales averaged over such heterogeneity, obscuring individual interprotein energy transfer steps. Here, we isolated and interrogated interprotein energy transfer by embedding two variants of the primary antenna protein from purple bacteria, light-harvesting complex 2 (LH2), together into a near-native membrane disc, known as a nanodisc. We integrated ultrafast transient absorption spectroscopy, quantum dynamics simulations, and cryogenic electron microscopy to determine interprotein energy transfer timescales. By varying the diameter of the nanodiscs, we replicated a range of distances between the proteins. The closest distance possible between neighboring LH2, which is the most common in native membranes, is 25 Šand resulted in a timescale of 5.7 ps. Larger distances of 28 to 31 Šresulted in timescales of 10 to 14 ps. Corresponding simulations showed that the fast energy transfer steps between closely spaced LH2 increase transport distances by ∼15%. Overall, our results introduce a framework for well-controlled studies of interprotein energy transfer dynamics and suggest that protein pairs serve as the primary pathway for the efficient transport of solar energy.

Real-time imaging of acoustic waves in bulk materials with X-ray microscopy.

The dynamics of lattice vibrations govern many material processes, such as acoustic wave propagation, displacive phase transitions, and ballistic thermal transport. The maximum velocity of these processes and their effects is determined by the speed of sound, which therefore defines the temporal resolution (picoseconds) needed to resolve these phenomena on their characteristic length scales (nanometers). Here, we present an X-ray microscope capable of imaging acoustic waves with subpicosecond resolution within mm-sized crystals. We directly visualize the generation, propagation, branching, and energy dissipation of longitudinal and transverse acoustic waves in diamond, demonstrating how mechanical energy thermalizes from picosecond to microsecond timescales. Bulk characterization techniques capable of resolving this level of structural detail have previously been available on millisecond time scales-orders of magnitude too slow to capture these fundamental phenomena in solid-state physics and geoscience. As such, the reported results provide broad insights into the interaction of acoustic waves with the structure of materials, and the availability of ultrafast time-resolved dark-field X-ray microscopy opens a vista of new opportunities for 3D imaging of materials dynamics on their intrinsic submicrosecond time scales.

A unified model for the dynamics of ATP-independent ultrafast contraction.

In nature, several ciliated protists possess the remarkable ability to execute ultrafast motions using protein assemblies called myonemes, which contract in response to Ca2+ ions. Existing theories, such as actomyosin contractility and macroscopic biomechanical latches, do not adequately describe these systems, necessitating development of models to understand their mechanisms. In this study, we image and quantitatively analyze the contractile kinematics observed in two ciliated protists (Vorticella sp. and Spirostomum sp.), and, based on the mechanochemistry of these organisms, we propose a minimal mathematical model that reproduces our observations as well as those published previously. Analyzing the model reveals three distinct dynamic regimes, differentiated by the rate of chemical driving and the importance of inertia. We characterize their unique scaling behaviors and kinematic signatures. Besides providing insights into Ca2+-powered myoneme contraction in protists, our work may also inform the rational design of ultrafast bioengineered systems such as active synthetic cells.

Direct mapping of bending and torsional dynamics in individual nanostructures.

Investigating coherent acoustic vibrations in nanostructured materials provides fundamental insights into optomechanical responses and microscopic energy flow. Extensive measurements of vibrational dynamics have been performed for a wide variety of nanoparticles and nanoparticle assemblies. However, virtually all of them show that only the dilation modes are launched after laser excitations, and the acoustic bending and torsional motions, which are commonly observed in photoexcited chemical bonds, are absent. Unambiguous identification and refined characterization of these "missing" modes have been a long-standing issue. In this report, we investigated the acoustic vibrational dynamics of individual Au nanoprisms on free-standing graphene substrates using an ultrafast high-sensitivity dark-field imaging approach in four-dimensional transmission electron microscopy. Following optical excitations, we observed low-frequency multiple-mode oscillations and higher superposition amplitudes at nanoprism corners and edges on the subnanoparticle level. In combination with finite-element simulations, we determined that these vibrational modes correspond to out-of-plane bending and torsional motions, superimposed by an overall tilting effect of the nanoprisms. The launch and relaxation processes of these modes are highly pertinent to substrate effects and nanoparticle geometries. These findings contribute to the fundamental understanding about acoustic dynamics of individual nanostructures and their interaction with substrates.

Specific and Nonuniform Brain States during Cold Perception in Mice.

The quest to decode the complex supraspinal mechanisms that integrate cutaneous thermal information in the central system is still ongoing. The dorsal horn of the spinal cord is the first hub that encodes thermal input which is then transmitted to brain regions via the spinothalamic and thalamocortical pathways. So far, our knowledge about the strength of the interplay between the brain regions during thermal processing is limited. To address this question, we imaged the brains of adult awake male mice in resting state using functional ultrasound imaging during plantar exposure to constant and varying temperatures. Our study reveals for the first time the following: (1) a dichotomy in the response of the somatomotor-cingulate cortices and the hypothalamus, which was never described before, due to the lack of appropriate tools to study such regions with both good spatial and temporal resolutions. (2) We infer that cingulate areas may be involved in the affective responses to temperature changes. (3) Colder temperatures (ramped down) reinforce the disconnection between the somatomotor-cingulate and hypothalamus networks. (4) Finally, we also confirm the existence in the mouse brain of a brain mode characterized by low cognitive strength present more frequently at resting neutral temperature. The present study points toward the existence of a common hub between somatomotor and cingulate regions, whereas hypothalamus functions are related to a secondary network.