title: A method for spatially resolved local intracellular mechanochemical sensing and organelle manipulation.
abstract: Because both the chemical and mechanical properties of living cells play crucial functional roles, there is a strong need for biophysical methods to address these properties simultaneously. Here we present a novel (to our knowledge) approach to measure local intracellular micromechanical and chemical properties using a hybrid magnetic chemical biosensor. We coupled a fluorescent dye, which serves as a chemical sensor, to a magnetic particle that is used for measurement of the viscoelastic environment by studying the response of the particle to magnetic force pulses. As a demonstration of the potential of this approach, we applied the method to study the process of phagocytosis, wherein cytoskeletal reorganization occurs in parallel with acidification of the phagosome. During this process, we measured the shear modulus and viscosity of the phagosomal environment concurrently with the phagosomal pH. We found that it is possible to manipulate phagocytosis by stalling the centripetal movement of the phagosome using magnetic force. Our results suggest that preventing centripetal phagosomal transport delays the onset of acidification. To our knowledge, this is the first report of manipulation of intracellular phagosomal transport without interfering with the underlying motor proteins or cytoskeletal network through biochemical methods.
authors.affiliation: Department of Nanobiophysics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Shekhar
authors.affiliation: Department of Nanobiophysics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands; Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Cambi
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.
authors.forename: C G
authors.initials: CG
authors.lastname: Figdor
authors.affiliation: Department of Nanobiophysics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: V
authors.initials: V
authors.lastname: Subramaniam
authors.affiliation: Department of Nanobiophysics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands. Electronic address: j.s.kanger@utwente.nl.
authors.forename: J S
authors.initials: JS
authors.lastname: Kanger
mesh_terms: D001696:Biomechanical Phenomena; D002470:Cell Survival; D006801:Humans; D006863:Hydrogen-Ion Concentration; D055595:Mechanical Phenomena; D055616:Microtechnology / Q000379:methods*; D010587:Phagocytosis; D010588:Phagosomes / Q000737:chemistry* / Q000378:metabolism; D012212:Rheology