Biology subjects

Salis, A.

Publications and source records attributed to Salis, A..

2 recordsLinked to original sources

bioRxiv2025

Buffer specificity of ionizable lipid nanoparticle transfection efficiency and bulk phase transition

Lipid nanoparticles (LNPs) are efficient and safe carriers for mRNA vaccines based on advanced ionizable lipids. It is understood that the pH dependent structural transition of the mesoscopic LNP core phase plays a key role in mRNA transfer. However, buffer specific variations in transfection efficiency remain obscure. Here we analyze the effect of buffer type on the structure and transfection efficiency of LNPs. We find that LNPs formulated with the cationic ionizable lipid DLin-MC3-DMA (MC3) in citrate compared to phosphate and acetate buffers exhibit earlier onset and stronger mRNA-GFP expression in-vitro. Using synchrotron small angle X-ray scattering (SAXS) we determine the pH dependent mesophases of ionizable lipid MC3/cholesterol/water dialyzed against the various buffers. The results show that the phase transition with decreasing pH from inverse micellar cubic to inverse hexagonal (Fd3m-HII) is shifted by one unit to a lower transition pH for acetate and phosphate compared to citrate buffer. Based on continuum theory and ion specific adsorption obtained from all-atom MD simulations, we propose a mechanism for buffer specificity. Citrate stabilizes the inverse hexagonal phase thus shifting the formation of HII to a higher pH. By contrast, phosphate and acetate stabilize LII. We propose that the Fd3m-to-HII transition, which is facilitated in citrate buffer, is responsible for a sensitized pH-response of the LNP core phase. This, in turn, enhances endosomal release efficiency and accounts for the earlier onset of gene expression observed in LNPs prepared with citrate buffer.

biophysics↗

bioRxiv2022

Acoustic cues and season affect mobbing responses in a bird community

Heterospecific communication is common for birds when mobbing a predator. However, joining the mob should depend on the number of callers already enrolled, as larger mobs imply lower individual risks for the newcomer. In addition, some community informant species seem more reliable regarding the information transferred in mobbing calls. Birds should therefore rely on both the number of callers and the species identity of the caller(s) when mobbing. In the present study, we tested the potential interaction between two acoustic cues. In a playback experiment, we modified the number of callers (through an increased number of calling individuals correlated to an increased duty cycle) and the emitter species (crested tits versus coal tits). Overall, we found that soundtracks with three callers triggered more mobbing than soundtracks with one caller and that soundtracks with coal tits calls triggered more mobbing than soundtracks with crested tits calls. Our results therefore support the hypothesis that birds consider both the species and the number of callers when joining a mobbing chorus in winter. Finally, we replicated the experiment in spring and did not record the same responses from the bird community. Indeed, only soundtracks with three coal tits triggered a mobbing response, suggesting therefore that the seasonal context can affect the results of studies on heterospecific communication. The potential mechanisms implicated in the varying responses to different acoustic cues and different seasons are discussed and should deserve further investigations.

ecology↗