Abstract

Langmuir-Blodgett (LB) thin films have been used as molecular bio-templates for facilitating macromolecular and protein crystallization, an approach pioneered by Pechkova and Nicolini in the early 2000s. LB-mediated crystallization has been found to lead to remarkable changes in protein stability and water dehydration, despite slight/negligible changes in protein atomic structure. We have previously discussed the importance of LB-based nanocrystallography at the frontiers of cancer proteomics focusing on two model proteins with important biological roles in cancer, which have been extensively studied and modeled, for investigating protein folding, disulfide bond formation, and protein dynamics, using protein crystallography or spectroscopy. These protein models are CK2alpha and RNase A. In particular, computational mutagenesis using the KINARI Mutagen webserver has shown to exhibit different behaviors in terms of protein stability and robustness, as well as in terms of water dynamics. Introduction of LB film seems to lead to the appearance of water molecules close to the protein surface with larger volume, causing changes in crystal stability, protective against radiation and appearing replicated in mutant proteins. Implications for drug design, drug delivery and cancer-causing protein variants are herein envisaged and discussed, along with a review of the most recent findings in LB-based nanobiocrystallography and with an overview of future prospects, including last developments and achievements in fabricating long-lasting drug delivery tools and spatiotemporally and sequentially-controlled drug releasing devices (the so-called “chronotherapeutics”).

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