Contents lists available at ScienceDirect BBA - Biomembranes journal homepage: www.elsevier.com/locate/bbamem Real-time monitoring of heat transfer between gold nanoparticles and tethered bilayer lipid membranes Amani Alghalayini a,e , Lele Jiang a ,XiGu b , Guan Heng Yeoh b , Charles G. Cranfield a,e , Victoria Timchenko b , Bruce A. Cornell c,e , Stella M. Valenzuela a,d,e, ⁎ a School of Life Sciences, University of Technology Sydney, Sydney, New South Wales 2007, Australia b School of Mechanical and Manufacturing Engineering, The University of New South Wales, Sydney, New South Wales 2052, Australia c Surgical Diagnostics Pty Ltd., Roseville, Sydney 2069, Australia d Institute for Biomedical Materials and Devices, University of Technology Sydney, Sydney, New South Wales 2007, Australia e ARC Research Hub for Integrated Devices for End-user Analysis at Low-levels (IDEAL), Faculty of Science, University of Technology Sydney, NSW 2007, Australia ARTICLEINFO Keywords: Tethered bilayer lipid membrane Gold nanoparticles Laser Heat transfer Hyperthermia Membrane dynamics Membrane proteins ABSTRACT Plasmon resonance frequency irradiated gold nanoparticles (GNPs) have gained interest as a laser-targeted treatment for infections, tumors and for the controlled release of drugs in situ. Questions still remain, however, as to the efficiency of heat delivery within biological tissues and how this can be reliably determined. Here, we demonstrate how a nanomaterial-electrode interface that mimics cell membranes can detect the localized heat transfer characteristics arising from plasmon resonance frequency-matched laser excitation of GNPs. We de- monstrate that the lipid bilayer membrane can be affected by conjugated GNP induced hyperthermia when irradiated with a laser power output as low as 135 nW/μm 2 . This is four orders of magnitude lower power than previouslyreported.Byrestrictingthelateralmovementofthelipidsinthebilayermembrane,itwasshownthat the change in membrane conductance as a result of the heat transfer was due to the creation of transient lipidic toroidal pores within the membrane. We further demonstrate that the heat transfer from the GNPs alters dif- fusionratesofmonomersofthegramicidin-Apeptidewithinthelipidleaflets.Thisworkhighlightshowtargeted low laser power GNP hyperthermia treatments, in vivo, could play a dual role of interfering with both cell membrane morphology and dynamics, along with membrane protein function. 1. Introduction Laser-induced gold nanoparticle (GNP) hyperthermia has emerged as a new class of minimally invasive, selective, targeted treatment for infection and tumors [1,2]. The application of GNPs in the therapeutics field and for imaging purposes arises from their unique, robust optical resonance absorption [3,4]. The temperature elevation of the GNPs is a consequence of electron oscillation due to light excitation of the na- nomaterials at their resonance wavelength [5]. Variable incident en- ergies such as near-infrared laser light [6],radiowaves[7]ormagnetic fields [8] can be utilized to excite the nanoparticles. Selective targeting of the GNPs can be achieved via surface functionalization with ligand moieties specific to an epitope or receptor. Laser-targeting of GNPs functionalized with specific antibodies directed against diseased cells has been shown to be effective and shows great promise as potential cancer therapy [9,10], to control neuronal function [11], to induce gene transfection [12] and to control the release of drugs in situ [13]. It is assumed that the photothermolysis phenomena is a con- sequence of heat released by the plasmonic nanoparticles that results in damage to cell membranes. This is believed to be the most likely out- come since lipid membranes are considered one of the most vulnerable sites within a cell. However, protein denaturation due to heating could also contribute to cell destruction [14]. Characterisation of the heat transfer from laser irradiation, at the appropriate plasmon resonance frequency for a single 30 nm diameter GNP and/or clusters of GNPs adjacent to lipid bilayers is challenging. Previous results suggest that exposure to an appropriate laser perpen- diculartothebilayernormal,inthemW/μm 2 range,cancausetransient nanopore formation or membrane rupture [15–17]. Yet it remains un- clear by what mechanism pore formation is induced by these hy- perthermal treatments. It has been shown that increased phospholipid disorder due to heating, might cause significant phase transitions within bilayer membranes [18]. Inthisstudy,itisshownthatananomaterial-electrodeinterfacethat https://doi.org/10.1016/j.bbamem.2020.183334 Received 11 February 2020; Received in revised form 25 April 2020; Accepted 28 April 2020 ⁎ Corresponding author at: School of Life Sciences, University of Technology Sydney, Sydney, New South Wales 2007, Australia. E-mail address: stella.valenzuela@uts.edu.au (S.M. Valenzuela). BBA - Biomembranes 1862 (2020) 183334 Available online 04 May 2020 0005-2736/ Crown Copyright © 2020 Published by Elsevier B.V. All rights reserved. T