L-3,4-Dihydroxyphenylalanine templated anisotropic gold nano/ micro-roses as potential disrupters/inhibitors of α-crystallin protein and its gleaned model peptide aggregates Avneet Kour a , Shikha Sharma a , Taru Dube a , Anjali Bisht a , Manju Sharma a , Jibanananda Mishra b , Md. Ehesan Ali a , Jiban Jyoti Panda a, ⁎ a Institute of Nano Science and Technology, Mohali, Punjab 160062, India b School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab 144411, India abstract article info Article history: Received 3 July 2020 Received in revised form 25 August 2020 Accepted 16 September 2020 Available online 19 September 2020 Keywords: Cataract α-Crystallin protein Disaggregation Amyloidogenic Gold nano/micro-roses Molecular dynamics simulation Cataract, the major cause of blindness worldwide occurs due to the misfolding and aggregation of the protein crystallin, which constitute a major portion of the lens protein. Other than the whole protein crystallin, the pep- tide sequences generated from crystallin as a result of covalent protein damage have also been shown to possess and foster protein aggregation, which can be established as crystallin aggregation models. Thus, the disaggrega- tion or inhibition of these protein aggregates could be a viable approach to combat cataract and preserve lens proteostasis. Herein, we tried to explore the disruption as well as inhibition of the intact α-crystallin protein and α-crystallin derived model peptide aggregates by L-3,4-dihydroxyphenylalanine (levodopa) coated gold (Au) nano/micro-roses as modulators. Thioflavin T fluorescence enhancement assay, and electron microscopic analysis were being employed to probe the anti-aggregation behavior of the Au nano/micro-roses towards the aggregating α-crystallin peptides/protein. Further, computational studies were performed to reveal the nature of molecular interactions between the levodopa molecule and the α-crystallin derived model peptides. Interest- ingly, both levodopa coated Au nano/micro-roses were found to be capable of inhibiting as well as preventing the aggregation of the intact α-crystallin protein and other model peptides derived from it. © 2020 Elsevier B.V. All rights reserved. 1. Introduction Ocular disorders like cataract account for the majority of cases of blindness (51%) [1]. Recently, as per WHO estimates, 65.2 million peo- ple suffer from cataract world-wide [2,3]. In developing countries like India, the total prevalence of blindness is around 1.1% and the main cause of this being cataract (62.6%) that affects almost over 9 million people [4]. Cataract can be defined as lens opacification leading to loss of visual acuity [5]. This is an age-related visual impairment disorder and is more prevalent in elderly persons [6]. Current cataract therapy lacks proper treatment modalities. Surgical removal of the opacified lens and substituting it with an artificial intraocular lens implant seems to be the only viable option for cataract therapy [7]. Around $6 billion are being spent every year on cataract surgery in the United States alone. However, surgery being invasive in nature comes with associated com- plications and is not feasible for every patient especially in most of the developing countries due to the scarcity of proper facilities, trained per- sonnel, and capital [7–9]. Cataract is generally caused by exogenous factors like ultraviolet radi- ation, trauma due to accidents and endogenous factors like diabetes and genetics [6]. Eye lens consists of three types of crystallin proteins such as α, β, and γ. These crystallin proteins lose solubility due to processes such as glycation or any other post-translational modification, leading to the accumulation of high molecular weight, non-transparent protein ag- gregates causing cataract [5]. The major pathological hallmark of cataract is protein aggregation like in the case of Alzheimer's disease, Parkinson's disease, Huntington disease, and type 2 diabetes. Thus, disaggregation of the crystallin protein aggregates could be a major treatment strategy for the disease. Gold nanoparticles (Au-NPs) are enormously used nanomaterials due to their interesting optical properties, excellent biocompatibility, easy fab- rication, and surface functionalization. Au-NPs have been shown to inhibit amyloid fibrillation in Alzheimer's disease and dissolve insulin amyloid aggregates in type 2 diabetes [10]. Small molecules and peptides have also represented the tendency to disrupt amyloid aggregates [11,12]. Au-NPs have been shown to exhibit maximum efficacy in disrupting am- yloid β aggregation in terms of substoichiometric ratios [13]. Levodopa has been shown to exhibit anti-amyloidogenic and fibril dis- aggregating potential against various amylodogenic proteins. It is reported that levodopa interfered with the fibrillogenesis of human lysozyme via International Journal of Biological Macromolecules 163 (2020) 2374–2391 ⁎ Corresponding author. E-mail address: jyoti@inst.ac.in (J.J. Panda). https://doi.org/10.1016/j.ijbiomac.2020.09.112 0141-8130/© 2020 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect International Journal of Biological Macromolecules journal homepage: http://www.elsevier.com/locate/ijbiomac