and visualization of the surface with BAM revealed a pronounced monolayer stabilization effect 10 with both quercetin and tiliroside, whereas rutin disrupted the monolayer structure rendering the 11 surface entirely smooth. SAXS showed a monotonous membrane thinning for all compounds 12 studied associated with an increase in the root mean square fluctuations of the membrane. Rutin, 13 quercetin and tiliroside decreased the bilayer thickness of DOPC by ~0.45 Å, 0.8 Å, and 1.1 Å at 14 6 mol %, respectively. In addition to the novelty of using lipid monolayers to systematically 15 characterize the structure activity relationship (SAR) of a variety of flavonoids; this is the first 16 report investigating the effect of tiliroside with biomimetic membrane models. All the flavonoids 17 studied are believed to be localized in the lipid/water interface region. Both this localization and 18 the membrane perturbations have implications for their therapeutic activity.

Cancer is a global problem with no sign that incidences are reducing. The great costs associated with curing cancer, through developing novel treatments and applying patented therapies, is an increasing burden to developed and developing nations alike. These financial and societal problems will be alleviated by research efforts into prevention, or treatments that utilise off-patent or repurposed agents. Phytosterols are natural components of the diet found in an array of seeds, nuts and vegetables and have been added to several consumer food products for the management of cardio-vascular disease through their ability to lower LDL-cholesterol levels. In this review, we provide a connected view between the fields of structural biophysics and cellular and molecular biology to evaluate the growing evidence that phytosterols impair oncogenic pathways in a range of cancer types. The current state of understanding of how phytosterols alter the biophysical properties of plasma membrane is described, and the potential for phytosterols to be repurposed from cardio-vascular to oncology therapeutics. Through an overview of the types of biophysical and molecular biology experiments that have been performed to date, this review informs the reader of the molecular and biophysical mechanisms through which phytosterols could have anti-cancer properties via their interactions with the plasma cell membrane. We also outline emerging and under-explored areas such as computational modelling, improved biomimetic membranes and ex vivo tissue evaluation. Focus of future research in these areas should improve understanding, not just of phytosterols in cancer cell biology but also to give insights into the interaction between the plasma membrane and the genome. These fields are increasingly providing meaningful biological and clinical data but iterative experiments between molecular biology assays, biosynthetic membrane studies and computational membrane modelling improve and refine our understanding of the role of different sterol components of the plasma membrane.

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