ArticleMatrix biology : journal of the International Society for Matrix Biology2016
Single molecule force measurements of perlecan/HSPG2: A key component of the osteocyte pericellular matrix.
Article in Matrix biology : journal of the International Society for Matrix Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- Mucosal Wound Repair: Reinforcement of Respiratory Mucus Barrier Function by Inorganic Polyphosphate.Progress in molecular and subcellular biology · 2026Review
- Ageing-Related Changes in Ultrastructural Bone Matrix Composition and Osteocyte Mechanosensitivity.Current osteoporosis reports · 2025Review
- Diverse and multifunctional roles for perlecan (JOR spine · 2024Review
- Dystroglycan-HSPG interactions provide synaptic plasticity and specificity.Glycobiology · 2024Review
- Perlecan, A Multi-Functional, Cell-Instructive, Matrix-Stabilizing Proteoglycan With Roles in Tissue Development Has Relevance to Connective Tissue Repair and Regeneration.Frontiers in cell and developmental biology · 2022Review
- Article
- High-resolution image-based simulation reveals membrane strain concentration on osteocyte processes caused by tethering elements.Biomechanics and modeling in mechanobiology · 2021Article
- Article
- Cleavage of the Perlecan-Semaphorin 3A-Plexin A1-Neuropilin-1 (PSPN) Complex by Matrix Metalloproteinase 7/Matrilysin Triggers Prostate Cancer Cell Dyscohesion and Migration.International journal of molecular sciences · 2021Article
- The mechanoresponse of bone is closely related to the osteocyte lacunocanalicular network architecture.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Network architecture strongly influences the fluid flow pattern through the lacunocanalicular network in human osteons.Biomechanics and modeling in mechanobiology · 2020Article
- Article
- Trabecular Bone Deficit and Enhanced Anabolic Response to Re-Ambulation after Disuse in Perlecan-Deficient Skeleton.Biomolecules · 2020Article
- Molecular mechanosensors in osteocytes.Bone research · 2020Review
- Mechanical Regulation of the Maternal Skeleton during Reproduction and Lactation.Current osteoporosis reports · 2019Review
- Dynamic Assembly of Human Salivary Stem/Progenitor Microstructures Requires Coordinated αFrontiers in cell and developmental biology · 2019Article
- Modular Proteoglycan Perlecan/Genes · 2018Review
- The heparan sulfate proteoglycan grip on hyperlipidemia and atherosclerosis.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
- Endorepellin remodels the endothelial transcriptome toward a pro-autophagic and pro-mitophagic gene signature.The Journal of biological chemistry · 2018Article
- Mesoscopic Rigid Body Modelling of the Extracellular Matrix Self-Assembly.Journal of integrative bioinformatics · 2018Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Perlecan/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.
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