RESUMEN
Loop formation in complex environments is crucially important to many biological processes in life. In the present work, we adopt three-dimensional Langevin dynamics simulations to investigate passive and active polymer looping kinetics in crowded media featuring polymer-crowder attraction. We find polymers undergo a remarkable coil-globule-coil transition, highlighted by a marked change in the Flory scaling exponent of the gyration radius. Meanwhile, looping time as a function of the crowder's volume fraction demonstrates an apparent non-monotonic alteration. A small number of crowders induce a compact structure, which largely facilitates the looping process. While a large number of crowders heavily impede end-to-end diffusion, looping kinetics is greatly inhibited. For a self-propelled chain, we find that the attractive crowding triggers an unusual activity effect on looping kinetics. Once a globular state is formed, activity takes an effort to open the chain from the compact structure, leading to an unexpected activity-induced inhibition of looping. If the chain maintains a coil state, the dominant role of activity is to enhance diffusivity and, thus, speed up looping kinetics. The novel conformational change and looping kinetics of both passive and active polymers in the presence of attractive crowding highlight a rather distinct scenario that has no analogy in a repulsive crowding counterpart. The underlying mechanism enriches our understanding of the crucial role of attractive interactions in modulating polymer structure and dynamics.
RESUMEN
A novel virus-like particle (VLP)-based multivalent recombinant human papillomavirus (HPV) vaccine was developed and evaluated in human, including 14 HPV-type specific VLP antigens (HPV6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59). The pseudovirus-based neutralizing assay (PBNA) method is widely used for immunogenicity assessment of HPV vaccine in clinical trials. However, as many as 14 antigen-specific antibody levels need be determined, PBNA is, for many reasons, challenging and time-consuming. In this study, we developed a Luminex immunological assay (LIA) and a competitive Luminex immunological assay (cLIA). These methods increase the throughput, reproducibility and precision, as well as reduce the complexity. All assay parameters showed good characteristics in the validation of both methods, benefiting from highly purified and structurally correct VLPs, high specific antibodies, standard VLP-microspheres and PE-mAbs conjugating process, adequate assay development and stable system. Validation data support the use of both methods for immunogenicity assessment in clinical trials. LIA showed higher sensitivity than cLIA, and due to limited epitopes of mAb, cLIA detected lower antibody responses, and therefore, fewer antibodies. This work not only supports clinical trials of 14-valent HPV vaccines more efficiently and reliably, but also provides a set of validation strategies and usable standards for general vaccine immunogenicity testing.
Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Humanos , Virus del Papiloma Humano , Infecciones por Papillomavirus/prevención & control , Reproducibilidad de los Resultados , Vacunas Combinadas , Anticuerpos Monoclonales , Antígenos ViralesRESUMEN
Extensive studies so far have indicated that chirality, anisotropic interactions and spatial confinement play important roles in collective dynamics in active matter systems. However, how the overall interplay of these crucial factors affects the novel phases and macroscopic properties remains less explored. Here, using Langevin dynamics simulations, we investigate the self-organization of a chiral active system composed of amphiphilic Janus particles, where the embedded anisotropic interaction orientation is assumed to be either the same or just opposite to the direction of active force. A wealth of dynamic phases are observed including formation of phase separation, clustering state, homogeneous state, spiral vortex flow, swarm and spatiotemporal oscillation. By tuning self-propelled angular speed and anisotropic interaction strength, we identify the non-equilibrium phase diagrams, and reveal the very non-trivial modulation of both vortex and swarm patterns. Intriguingly, we find that strong chirality-alignment-confinement coupling yields a self-driven spatial and temporal organization periodically oscillating between a counterclockwise vortex and a clockwise one. Our work provides a new understanding of the novel self-assembly arising in such a confined system and enables new strategies for achieving ordered dynamic structures.
RESUMEN
Active filament translocation through a confined space is crucial for diverse biological processes. By using Langevin dynamics simulations, we investigate the translocation dynamics of an axially self-propelled chain through a channel. First, results show a suggestive reciprocal scaling of translocation time versus active force. Second, in the case of a long channel, we demonstrate a very intriguing nonmonotonic change of translocation time with increasing channel width. The driving force shows a similar trend, providing a consistent picture to understand the unexpected channel width effect. In particular, in a moderately broad channel, the disordered chain conformation results in a loss of driving force and thus inhibits translocation dynamics. Chain adsorption might occur in a wide channel, which accounts for a facilitated translocation. Lastly, we connect the translocation process to tension propagation (TP). A modified TP picture is proposed to interpret the waiting time distribution. Our work highlights the new phenomenology owing to the crucial interplay of activity and spacial confinement, which drives the translocation dynamics, going beyond the traditional entropic barrier scenario.