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Abstract
We outline the factors involved in precise targeting of lipids and membranes by probes, namely, lipid and probe chemistry, geometry/topography of probe delivery, and probe uptake kinetics. The special case of probe orientation within membranes also is considered. The varieties of commercially available fluorophores are described, and an overview of probe physicochemical properties (amphiphilicity, conjugated system size, electrical properties, head group size, lipophilicity and solubility) is provided together with notes on their parameterization. Probe-lipid physicochemical interactions, and their relations to parameterization, then are discussed including the nature and derivation of decision-rule QSAR models, partitioning and insertion of probes into bulk lipids and complications of this, partitioning and insertion of probes into membranes, and flip-flop of probes across membrane leaflets. A general QSAR algorithm for understanding lipid probe application then is set out. Problems and limitations are outlined. Biological issues include varied biomembrane composition, cell line effects and toxicity of fluorescent probes. Methodological issues include difficulties of estimating certain numerical structure parameters, the impure character of many fluorochromes and dyes, and the perturbation of biomembrane structure by fluorescent probes.
Acknowledgments
We thank Prof. Ian McGrath, School of Life Sciences, Glasgow University, Scotland for providing facilities and Dr. David W. Deamer for the graphic inspiring . The collaboration of Dr. Alfonso Blázquez-Castro, Adriana Casas, Magdalena Cañete, Lorena G. Rodríguez, and Angeles Villanueva also is acknowledged.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.