Deformable microlaser force sensingOACSTPCD
Deformable microlaser force sensing
Mechanical forces are key regulators of cellular behavior and function,affecting many fundamental biological processes such as cell migration,embryogenesis,immunological responses,and pathological states.Specialized force sensors and imaging techniques have been developed to quantify these otherwise invisible forces in single cells and in vivo.However,current techniques rely heavily on high-resolution microscopy and do not allow interrogation of optically dense tissue,reducing their application to 2D cell cultures and highly transparent biological tissue.Here,we introduce DEFORM,deformable microlaser force sensing,a spectroscopic technique that detects sub-nanonewton forces with unprecedented spatio-temporal resolution.DEFORM is based on the spectral analysis of laser emission from dye-doped oil microdroplets and uses the force-induced lifting of laser mode degeneracy in these droplets to detect nanometer deformations.Following validation by atomic force microscopy and development of a model that links changes in laser spectrum to applied force,DEFORM is used to measure forces in 3D and at depths of hundreds of microns within tumor spheroids and late-stage Drosophila larva.We furthermore show continuous force sensing with single-cell spatial and millisecond temporal resolution,thus paving the way for non-invasive studies of biomechanical forces in advanced stages of embryogenesis,tissue remodeling,and tumor invasion.
Eleni Dalaka;Joseph S.Hill;Jonathan H.H.Booth;Anna Popczyk;Stefan R.Pulver;Malte C.Gather;Marcel Schubert
Centre of Biophotonics,SUPA,School of Physics and Astronomy,University of St Andrews,North Haugh,St Andrews,UK||Institute for Bioengineering of Catalonia,Barcelona,SpainCentre of Biophotonics,SUPA,School of Physics and Astronomy,University of St Andrews,North Haugh,St Andrews,UK||Humboldt Centre for Nano-and Biophotonics,Department of Chemistry,University of Cologne,Köln,GermanyHumboldt Centre for Nano-and Biophotonics,Department of Chemistry,University of Cologne,Köln,Germany||School of Psychology and Neuroscience,University of St Andrews,St Mary's Quad,South Street,St Andrews,UKHumboldt Centre for Nano-and Biophotonics,Department of Chemistry,University of Cologne,Köln,GermanySchool of Psychology and Neuroscience,University of St Andrews,St Mary's Quad,South Street,St Andrews,UK
《光：科学与应用（英文版）》 2024 (006)
1196-1209 / 14
We thank Dr.Christian Jüngst and Dr.Jens Peter Gabriel from the CECAD Imaging Facility and Leica Microsystems,respectively,for their support with multi photon microscopy.We thank Yury Demchenko for fruitful discussions.This work received financial support from EPSRC(EP/P030017/1),the Humboldt Foundation(Alexander von Humboldt Professorship),European Union's Horizon 2020 Framework Programme(FP/2014-2020)/ERC grant agreement no.640012(ABLASE),Deutsche Forschungsgemeinschaft(469988234),and instrument funding by the Deutsche Forschungsgemeinschaft in cooperation with the Ministerium für Kunst und Wissenschaft of North Rhine-Westphalia(INST 216/1120-1 FUGG).MS acknowledges funding by the Royal Society(Dorothy Hodgkin Fellowship,DH160102;Enhancement Award,RGF\EA\180051).
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