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Biological membranes are complex, heterogeneous, and dynamic systems that play roles in the compartmentalization and protection of cells from the environment. It is still a challenge to elucidate kinetics and real-time transport routes for molecules through biological membranes in live cells. Currently, by developing and employing super-resolution microscopy; increasing evidence indicates channels and transporter nano-organization and dynamics within membranes play an important role in these regulatory mechanisms. Here we review recent advances and discuss the major advantages and disadvantages of using super-resolution microscopy to investigate protein organization and transport within plasma membranes.

Hypothesis: Amphotericin B (AmB) is a highly effective antimicrobial, with broad antimycotic and antiparasitic effect. However, AmB poor water-solubilisation and aggregation tendency limits its use for topical applications. We studied the capacity of nanostructures formed by alkyl esters of L-ascorbic acid (ASCn) to solubilise AmB and tested the relationship between the prevalence of the monomeric form of AmB and its effectiveness as antimicrobial agent. Experiments: We developed self-assembled nanostructures formed by the commercial compound, palmitoyl ascorbic acid, as well as the shorter chained myristoyl and lauroyl ascorbic acid. AmB loaded ASCn nanostructures were studied by a combination of spectroscopic techniques, together with particle analysis, differential scanning calorimetry, microbiological tests, and Langmuir monolayer visualisation. Findings: We found no direct relation between the antimicrobial capacity and the prevalence of the monomeric form of the drug. However, the later was related to chemical stability and colloidal robustness. Nanostructures formed by ASC16 in its anionic state provide an appropriate environment for AmB in its monomeric form, maintaining its antimicrobial capacity. Langmuir film visualisation supports spectrophotometric evidence, indicating that ASC16 allows the in-plane solubilisation of AmB. Coagels formed by ASC16 appear as promising for carrying AmB for dermal delivery.

Cell membranes develop extraordinarily complex lipids and proteins geared to perform functions required by cells [...]