Liquid Crystal Enabled Early Stage Detection of Beta Amyloid Formation on Lipid Monolayers

Abstract

Liquid crystals (LCs) can serve as sensitive reporters of interfacial events, and this property has been used for sensing of synthetic or biological toxins. Here it is demonstrated that LCs can distinguish distinct molecular motifs and exhibit a specific response to beta‐sheet structures. That property is used to detect the formation of highly toxic protofibrils involved in neurodegenerative diseases, where it is crucial to develop methods that probe the early‐stage aggregation of amyloidogenic peptides in the vicinity of biological membranes. In the proposed method, the amyloid fibrils formed at the lipid–decorated LC interface can change the orientation of LCs and form elongated and branched structures that are amplified by the mesogenic medium; however, nonamyloidogenic peptides form ellipsoidal domains of tilted LCs. Moreover, a theoretical and computational analysis is used to reveal the underlying structure of the LC, thereby providing a detailed molecular‐level view of the interactions and mechanisms responsible for such motifs. The corresponding signatures can be detected at nanomolar concentrations of peptide by polarized light microscopy and much earlier than the ones that can be identified by fluorescence‐based techniques. As such, it offers the potential for early diagnoses of neurodegenerative diseases and for facile testing of inhibitors of amyloid formation.

Functional Liquid Crystals towards the Next Generation of Materials

“…[164,185] Sensing systems using amphiphilic surfactants and nematic liquid crystals have been developed by Abbott and co-workers. [164,[186][187][188][189][190][191] These sensors are classified as thin-film type (Figure 9) [186][187][188][189] or droplet type. [190,191] Forthe thin-film type,the LC layer was embedded in ag old grid on ag lass substrate soaked in aw ater solution and surfactants self-assembled at the interfaces between the LC phase and aqueous phase align the bulk LC molecules homeotropically.…”

“…[190,191] Forthe thin-film type,the LC layer was embedded in ag old grid on ag lass substrate soaked in aw ater solution and surfactants self-assembled at the interfaces between the LC phase and aqueous phase align the bulk LC molecules homeotropically. [186][187][188][189] Fort he droplet type,l iquid crystals were encapsulated in polymeric surfactant microcapsules. [190,191] Thed roplet sensors show high biocompatibility.…”

“…Reviews such as Alzheimers) [188] and quantifying of exposure to bacterial endotoxin (a major cause of disease and contamination) at pg mL À1 concentrations. [190] Dynamic and ordered states of nematic liquid crystals can be applied for the preparation of LC actuators, [165] as well as optical materials.P olymer films with well-organized molecular order were obtained by Broer and co-workers based on photopolymerization of LC monomers containing an infrared (IR)-absorbing dye on patterned alignment layers.…”

Liquid Crystal Biosensors: New Approaches

“…Recently, LCs have been explored for the design of interfaces that mediate desired interactions with biological systems (Lowe and Abbott, 2012). LC materials allow label-free observations of biological phenomena as the orientational properties of LCs enable the amplification and the transduction of biologically relevant binding events at nanostructured surfaces into optical outputs visible by naked eye (Brake et al, 2003a; Lin et al, 2011;Brake and Abbott, 2002; Brake et al, 2003b; Lockwood et al, 2005; Price and Schwartz, 2008;Brake et al, 2005; Lockwood et al, 2006;Sivakumar et al, 2009;Gupta et al, 2009; Park and Abbott, 2008; Hu and Jang, 2012;Bai et al, 2014; Khan and Park, 2014;Sadati et al, 2015;Zhu and Yang, 2015;Wang et al, 2015; Munir et al, 2015). The study of biomolecular interaction using LC material relies on the interaction between the sensing LC and the biomolecule of interest.…”

Substoichiometric molecular control and amplification of the initiation and nature of amyloid fibril formation: lessons from and for blood clotting

“…The same was true for molecular mimics of LPS [398]. Indeed, different liquid crystals can also be used as 'biosensors' [399] to detect β-amyloid formation [400], protein-LPS interactions [401] and microvesicles [402].…”