Viscoelasticity of amyloid plaques in transgenic mouse brain studied by Brillouin microspectroscopy and correlative Raman analysis

A myloidopathy is one of the most prominent hallmarks of Alkheimer's disease(AD),the leading cause of dementia worldwide,and is characterized by the accumulation of amyloid plaques in the brain parenchyma.The plaques consist of abnornal deposits mainly composed of an aggregation-prone protein fragment,B-amyloid 140/1-42,into the extracellular matrix.Brillouin micro-spectroscopy is an all-optical contactless technique that is based on the interaction between visible light and longitudinal acoustic waves or phonons,giving access to the viscoelasticity of a sample on a subcellular scale.Here,we describe the first application of micromechanical mapping based on Brillouin scattering spectroscopy to probe the stifness of individual amyloid plaques in the hippocampal part of the brain of a B-amyloid overexpressi ng transgenic mouse.Correlative analysis based on Brillouin and Raman microspectroscopy showed that amyloid plaques have a complex structure with a rigid core of B-pleated shoet conformation(B-aryloid)protein sur-rounded by a softer ring-shaped region richer in lipids and other protein conformations.These preliminary results give a new insight into the plaque biophysics and biomechanics,and a valuable contrast mechanism for the study and diagnosis of amnyloidopathy.

Non-contact mechanical and chemical analysis of single living cells by microspectroscopic techniques

Innovative label-free microspectroscopy,which can simultaneously collect Brillouin and Raman signals,is used to characterize the viscoelastic properties and chemical composition of living cells with sub-micrometric resolution.The unprecedented statistical accuracy of the data combined with the high-frequency resolution and the high contrast of the recently built experimental setup permits the study of single living cells immersed in their buffer solution by contactless measurements.The Brillouin signal is deconvoluted in the buffer and the cell components,thereby revealing the mechanical heterogeneity inside the cell.In particular,a 20%increase is observed in the elastic modulus passing from the plasmatic membrane to the nucleus as distinguished by comparison with the Raman spectroscopic marker.Brillouin line shape analysis is even more relevant for the comparison of cells under physiological and pathological conditions.Following oncogene expression,cells show an overall reduction in the elastic modulus(15%)and apparent viscosity(50%).In a proof-of-principle experiment,the ability of this spectroscopic technique to characterize subcellular compartments and distinguish cell status was successfully tested.The results strongly support the future application of this technique for fundamental issues in the biomedical field.