Single molecule force measurements of perlecan/HSPG2: A key component of the osteocyte pericellular matrix

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dc.citation.firstpage27en_US
dc.citation.journalTitleMatrix Biologyen_US
dc.citation.lastpage38en_US
dc.citation.volumeNumber50en_US
dc.contributor.authorWijeratne, Sithara S.en_US
dc.contributor.authorMartinez, Jerahme R.en_US
dc.contributor.authorGrindel, Brian J.en_US
dc.contributor.authorFrey, Eric W.en_US
dc.contributor.authorLi, Jingqiangen_US
dc.contributor.authorWang, Liyunen_US
dc.contributor.authorFarach-Carson, Mary C.en_US
dc.contributor.authorKiang, Ching-Hwaen_US
dc.contributor.orgBioengineeringen_US
dc.contributor.orgBiosciencesen_US
dc.contributor.orgPhysics and Astronomyen_US
dc.date.accessioned2017-05-03T19:58:19Zen_US
dc.date.available2017-05-03T19:58:19Zen_US
dc.date.issued2016en_US
dc.description.abstractPerlecan/HSPG2, a large, monomeric heparan sulfate proteoglycan (HSPG), is a key component of the lacunar canalicular system (LCS) of cortical bone, where it is part of the mechanosensing pericellular matrix (PCM) surrounding the osteocytic processes and serves as a tethering element that connects the osteocyte cell body to the bone matrix. Within the pericellular space surrounding the osteocyte cell body, perlecan can experience physiological fluid flow drag force and in that capacity function as a sensor to relay external stimuli to the osteocyte cell membrane. We previously showed that a reduction in perlecan secretion alters the PCM fiber composition and interferes with bone's response to a mechanical loading in vivo. To test our hypothesis that perlecan core protein can sustain tensile forces without unfolding under physiological loading conditions, atomic force microscopy (AFM) was used to capture images of perlecan monomers at nanoscale resolution and to perform single molecule force measurement (SMFMs). We found that the core protein of purified full-length human perlecan is of suitable size to span the pericellular space of the LCS, with a measured end-to-end length of 170 ± 20 nm and a diameter of 2–4 nm. Force pulling revealed a strong protein core that can withstand over 100 pN of tension well over the drag forces that are estimated to be exerted on the individual osteocyte tethers. Data fitting with an extensible worm-like chain model showed that the perlecan protein core has a mean elastic constant of 890 pN and a corresponding Young's modulus of 71 MPa. We conclude that perlecan has physical properties that would allow it to act as a strong but elastic tether in the LCS.en_US
dc.identifier.citationWijeratne, Sithara S., Martinez, Jerahme R., Grindel, Brian J., et al.. "Single molecule force measurements of perlecan/HSPG2: A key component of the osteocyte pericellular matrix." <i>Matrix Biology,</i> 50, (2016) Elsevier: 27-38. https://doi.org/10.1016/j.matbio.2015.11.001.en_US
dc.identifier.doihttps://doi.org/10.1016/j.matbio.2015.11.001en_US
dc.identifier.urihttps://hdl.handle.net/1911/94145en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.en_US
dc.subject.keywordPerlecanen_US
dc.subject.keywordHeparan sulfate proteoglycanen_US
dc.subject.keywordAtomic force microscopyen_US
dc.subject.keywordOsteocytesen_US
dc.subject.keywordLacunar canalicular systemen_US
dc.subject.keywordBoneen_US
dc.titleSingle molecule force measurements of perlecan/HSPG2: A key component of the osteocyte pericellular matrixen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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