Liquid crystals and neuro-degenerative diseases
Liquid crystals are familiar to most of us as the somewhat humdrum stuff used to make computer displays and TVs. Even for scientists, it has not been easy to find other uses.
Now a group of researchers led by Argonne Senior Scientist Juan de Pablo at the Institute for Molecular Engineering is putting liquid crystals to work in a completely unexpected realm: as detectors for the protein fibers implicated in the development of neuro-degenerative diseases such as Alzheimer’s.
Their novel approach promises an easier, less costly way to detect these fibers and to do so at a much earlier stage of their formation than has been possible before—the stage when they are thought to be the most toxic.
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.
Monirosadat Sadati, Aslin Izmitli Apik, Julio C. Armas-Perez, Jose Martinez-Gonzalez, Juan P. Hernandez-Ortiz,
Nicholas L. Abbott and Juan J. de Pablo, “Liquid Crystal Enabled Early Stage Detection of Beta Amyloid Formation on Lipid Monolayers,” Advanced Functional Materials (2015). DOI: 10.1002/adfm.201502830. Published Online September 9, 2015.