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

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dc.citation.firstpage27
dc.citation.journalTitleMatrix Biology
dc.citation.lastpage38
dc.citation.volumeNumber50
dc.contributor.authorWijeratne, Sithara S.
dc.contributor.authorMartinez, Jerahme R.
dc.contributor.authorGrindel, Brian J.
dc.contributor.authorFrey, Eric W.
dc.contributor.authorLi, Jingqiang
dc.contributor.authorWang, Liyun
dc.contributor.authorFarach-Carson, Mary C.
dc.contributor.authorKiang, Ching-Hwa
dc.date.accessioned2017-05-03T19:58:19Z
dc.date.available2017-05-03T19:58:19Z
dc.date.issued2016
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.
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.
dc.identifier.doihttps://doi.org/10.1016/j.matbio.2015.11.001
dc.identifier.urihttps://hdl.handle.net/1911/94145
dc.language.isoeng
dc.publisherElsevier
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.
dc.subject.keywordPerlecan
dc.subject.keywordHeparan sulfate proteoglycan
dc.subject.keywordAtomic force microscopy
dc.subject.keywordOsteocytes
dc.subject.keywordLacunar canalicular system
dc.subject.keywordBone
dc.titleSingle molecule force measurements of perlecan/HSPG2: A key component of the osteocyte pericellular matrix
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpost-print
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