Autologous Gradient Formation under Differential Interstitial Fluid Flow Environments
Abstract
:1. Introduction
2. Materials and Methods
2.1. Assumptions of the Model
2.2. Equations and Implementation of the Model
2.3. Conditions and Quantitative Values Used in the Model
3. Results
3.1. Effects of Transport Parameter Changes on Pericellular Gradients
3.2. Directionality of Flow Alters Gradient
3.3. Temporal Fluctuations in Velocity Yield Variable Gradients
3.4. Background Concentration Can Negate Bound CXCL12 Gradient
3.5. The Invading Cell Needs to Be a Certain Distance from Tumor Border for Gradient to Develop
3.6. Cell Type and Morphology Affects Gradient Formation
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
- Barnes, J.M.; Przybyla, L.; Weaver, V.M. Tissue Mechanics Regulate Brain Development, Homeostasis and Disease. J. Cell Sci. 2017, 130, 71–82. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Orr, A.W.; Helmke, B.P.; Blackman, B.R.; Schwartz, M.A. Mechanisms of Mechanotransduction. Dev. Cell 2006, 10, 11–20. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Polacheck, W.J.; German, A.E.; Mammoto, A.; Ingber, D.E.; Kamm, R.D. Mechanotransduction of Fluid Stresses Governs 3D Cell Migration. Proc. Natl. Acad. Sci. USA 2014, 111, 2447–2452. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Miller, R.J.; Rostene, W.; Apartis, E.; Banisadr, G.; Biber, K.; Milligan, E.D.; White, F.A.; Zhang, J. Chemokine Action in the Nervous System. J. Neurosci. 2008, 28, 11792–11795. [Google Scholar] [CrossRef]
- Wang, J.; Knaut, H. Chemokine Signaling in Development and Disease. Development 2014, 141, 4199–4205. [Google Scholar] [CrossRef] [Green Version]
- Moore, J.E.; Brook, B.S.; Nibbs, R.J.B. Chemokine Transport Dynamics and Emerging Recognition of Their Role in Immune Function. Curr. Opin. Biomed. Eng. 2018, 5, 90–95. [Google Scholar] [CrossRef] [PubMed]
- Munson, J.M.; Shieh, A.C. Interstitial Fluid Flow in Cancer: Implications for Disease Progression and Treatment. Cancer Manag. Res. 2014, 6, 317–318. [Google Scholar] [CrossRef] [Green Version]
- Wagner, M.; Wiig, H. Tumor Interstitial Fluid Formation, Characterization, and Clinical Implications. Front. Oncol. 2015, 5, 115. [Google Scholar] [CrossRef] [Green Version]
- Müller, A.; Homey, B.; Soto, H.; Ge, N.; Catron, D.; Buchanan, M.E.; McClanahan, T.; Murphy, E.; Yuan, W.; Wagner, S.N.; et al. Involvement of Chemokine Receptors in Breast Cancer Metastasis. Nature 2001, 410, 50–56. [Google Scholar] [CrossRef]
- Kingsmore, K.M.; Vaccari, A.; Abler, D.; Cui, S.X.; Epstein, F.H.; Rockne, R.C.; Acton, S.T.; Munson, J.M. MRI Analysis to Map Interstitial Flow in the Brain Tumor Microenvironment. APL Bioeng. 2018, 2, 031905. [Google Scholar] [CrossRef]
- Shetty, A.K.; Zanirati, G. The Interstitial System of the Brain in Health and Disease. Aging Dis. 2020, 11, 200–211. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Iliff, J.J.; Wang, M.; Liao, Y.; Plogg, B.A.; Peng, W.; Gundersen, G.A.; Benveniste, H.; Vates, G.E.; Deane, R.; Goldman, S.A.; et al. A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid b. Sci. Transl. Med. 2012, 4, 147ra111. [Google Scholar] [CrossRef] [Green Version]
- Weller, R.O. Pathology of Cerebrospinal Fluid and Interstitial Fluid of the CNS: Significance for Alzheimer Disease, Prion Disorders and Multiple Sclerosis. J. Neuropathol. Exp. Neurol. 1998, 57, 885–894. [Google Scholar] [CrossRef] [Green Version]
- Kingsmore, K.M.; Logsdon, D.K.; Floyd, D.H.; Peirce, S.M.; Purow, B.W.; Munson, J.M. Interstitial Flow Differentially Increases Patient-Derived Glioblastoma Stem Cell Invasion: Via CXCR4, CXCL12, and CD44-Mediated Mechanisms. Integr. Biol. 2016, 8, 1246–1260. [Google Scholar] [CrossRef]
- Shieh, A.C.; Swartz, M.A. Regulation of Tumor Invasion by Interstitial Fluid Flow. Phys. Biol. 2011, 8, 015012. [Google Scholar] [CrossRef]
- Boucher, Y.; Salehi, H.; Witwer, B.; Harsh, G.R.; Jain, R.K. Interstitial Fluid Pressure in Intracranial Tumours in Patients and in Rodents. Br. J. Cancer 1997, 75, 829–836. [Google Scholar] [CrossRef] [PubMed]
- Cornelison, R.C.; Brennan, C.E.; Kingsmore, K.M.; Munson, J.M. Convective Forces Increase CXCR4-Dependent Glioblastoma Cell Invasion in GL261 Murine Model. Sci. Rep. 2018, 8, 17057. [Google Scholar] [CrossRef] [Green Version]
- Munson, J.M.; Bellamkonda, R.V.; Swartz, M.A. Interstitial Flow in a 3d Microenvironment Increases Glioma Invasion by a Cxcr4-Dependent Mechanism. Cancer Res. 2013, 73, 1536–1546. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Balkwill, F. Cancer and the Chemokine Network. Nat. Rev. Cancer 2004, 4, 540–550. [Google Scholar] [CrossRef]
- Lacalle, R.A.; Blanco, R.; Carmona-Rodríguez, L.; Martín-Leal, A.; Mira, E.; Mañes, S. Chemokine Receptor Signaling and the Hallmarks of Cancer. Int. Rev. Cell Mol. Biol. 2017, 331, 181–244. [Google Scholar] [CrossRef]
- Shields, J.D.; Randolph, G.J.; Fleury, M.E.; Yong, C.; Swartz, M.A.; Tomei, A.A. Autologous Chemotaxis as a Mechanism of Tumor Cell Homing to Lymphatics via Interstitial Flow and Autocrine CCR7 Signaling. Cancer Cell 2007, 11, 526–538. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Loberg, R.D.; Day, L.S.L.; Harwood, J.; Ying, C.; St. John, L.N.; Giles, R.; Neeley, C.K.; Pienta, K.J. CCL2 Is a Potent Regulator of Prostate Cancer Cell Migration and Proliferation. Neoplasia 2006, 8, 578–586. [Google Scholar] [CrossRef] [Green Version]
- Laguri, C.; Arenzana-Seisdedos, F.; Lortat-Jacob, H. Relationships between Glycosaminoglycan and Receptor Binding Sites in Chemokines-the CXCL12 Example. Carbohydr. Res. 2008, 343, 2018–2023. [Google Scholar] [CrossRef] [PubMed]
- Netelenbos, T.; Zuijderduijn, S.; van den Born, J.; Kessler, F.; Zweegman, S.; Huijgens, P.C.; Dräger, A.M. Proteoglycans Guide SDF-1-induced Migration of Hematopoietic Progenitor cells. J. Leukoc. Biol. 2002, 72, 353–362. [Google Scholar]
- Barinov, A.; Luo, L.; Gasse, P.; Meas-Yedid, V.; Donnadieu, E.; Arenzana-Seisdedos, F.; Vieira, P. Essential Role of Immobilized Chemokine CXCL12 in the Regulation of the Humoral Immune Response. Proc. Natl. Acad. Sci. USA 2017, 114, 2319–2324. [Google Scholar] [CrossRef] [Green Version]
- Logun, M.T.; Bisel, N.S.; Tanasse, E.A.; Zhao, W.; Gunasekera, B.; Mao, L.; Karumbaiah, L. Glioma Cell Invasion Is Significantly Enhanced in Composite Hydrogel Matrices Composed of Chondroitin 4- and 4,6-Sulfated Glycosaminoglycans. J. Mater. Chem. B 2016, 4, 6052–6064. [Google Scholar] [CrossRef] [Green Version]
- Thakar, D.; Dalonneau, F.; Migliorini, E.; Lortat-Jacob, H.; Boturyn, D.; Albiges-Rizo, C.; Coche-Guerente, L.; Picart, C.; Richter, R.P. Binding of the Chemokine CXCL12α to Its Natural Extracellular Matrix Ligand Heparan Sulfate Enables Myoblast Adhesion and Facilitates Cell Motility. Biomaterials 2017, 123, 24–38. [Google Scholar] [CrossRef]
- Levicar, N.; Nutall, R.K.; Lah, T.T. Proteases in Brain Tumour Progression. Acta Neurochir. 2003, 145, 825–838. [Google Scholar] [CrossRef] [PubMed]
- Rao, J.S. Molecular Mechanisms of Glioma Invasiveness: The Role of Proteases. Nat. Rev. Cancer 2003, 3, 489–501. [Google Scholar] [CrossRef]
- Sadir, R.; Imberty, A.; Baleux, F.; Lortat-Jacob, H. Heparan Sulfate/Heparin Oligosaccharides Protect Stromal Cell-Derived Factor-1 (SDF-1)/CXCL12 against Proteolysis Induced by CD26/Dipeptidyl Peptidase IV. J. Biol. Chem. 2004, 279, 43854–43860. [Google Scholar] [CrossRef] [Green Version]
- Janssens, R.; Struyf, S.; Proost, P. The Unique Structural and Functional Features of CXCL12. Cell. Mol. Immunol. 2018, 15, 299–311. [Google Scholar] [CrossRef]
- McQuibban, G.A.; Butler, G.S.; Gong, J.H.; Bendall, L.; Power, C.; Clark-Lewis, I.; Overall, C.M. Matrix Metalloproteinase Activity Inactivates the CXC Chemokine Stromal Cell-Derived Factor-1. J. Biol. Chem. 2001, 276, 43503–43508. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Saw, S.; Weiss, A.; Khokha, R.; Waterhouse, P.D. Metalloproteases: On the Watch in the Hematopoietic Niche. Trends Immunol. 2019, 40, 1053–1070. [Google Scholar] [CrossRef] [Green Version]
- Fleury, M.E.; Boardman, K.C.; Swartz, M.A. Autologous Morphogen Gradients by Subtle Interstitial Flow and Matrix Interactions. Biophys. J. 2006, 91, 113–121. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Waldeland, J.O.; Evje, S. A Multiphase Model for Exploring Tumor Cell Migration Driven by Autologous Chemotaxis. Chem. Eng. Sci. 2018, 191, 268–287. [Google Scholar] [CrossRef]
- Jafarnejad, M.; Zawieja, D.C.; Brook, B.S.; Nibbs, R.J.B.; Moore, J.E. A Novel Computational Model Predicts Key Regulators of Chemokine Gradient Formation in Lymph Nodes and Site-Specific Roles for CCL19 and ACKR4. J. Immunol. 2017, 199, 2291–2304. [Google Scholar] [CrossRef] [Green Version]
- Chang, S.L.; Cavnar, S.P.; Takayama, S.; Luker, G.D.; Linderman, J.J. Cell, Isoform, and Environment Factors Shape Gradients and Modulate Chemotaxis. PLoS ONE 2015, 10, e0174189. [Google Scholar] [CrossRef] [Green Version]
- Fournier, R. Basic Transport. Phenomena in Biomedical Engineering, 3rd ed.; CRC Press: Boca Raton, FL, USA, 2011. [Google Scholar]
- Lui, A.C.P.; Polis, T.Z.; Cicutti, N.J. Densities of Cerebrospinal Fluid and Spinal Anaesthetic Solutions in Surgical Patients at Body Temperature. Can. J. Anaesth. 1998, 45, 297–303. [Google Scholar] [CrossRef] [Green Version]
- Bloomfield, I.G.; Johnston, I.H.; Bilston, L.E. Effects of Proteins, Blood Cells and Glucose on the Viscosity of Cerebrospinal Fluid. Pediatr. Neurosurg. 1998, 28, 246–251. [Google Scholar] [CrossRef]
- Linninger, A.A.; Tsakiris, C.; Zhu, D.C.; Xenos, M.; Roycewicz, P.; Danziger, Z.; Penn, R. Pulsatile Cerebrospinal Fluid Dynamics in the Human Brain. IEEE Trans. Biomed. Eng. 2005, 52, 557–565. [Google Scholar] [CrossRef]
- Chatterjee, K.; Atay, N.; Abler, D.; Bhargava, S.; Sahoo, P.; Rockne, R.; Munson, J. Utilizing Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to Analyze Interstitial Fluid Flow and Transport in Glioblastoma and the Surrounding Parenchyma in Human Patients. Pharmaceutics 2021, 13, 212. [Google Scholar] [CrossRef]
- Corzo, J.; Santamaria, M. Time, the Forgotten Dimension of Ligand Binding Teaching. Biochem. Mol. Biol. Educ. 2006, 34, 413–416. [Google Scholar] [CrossRef]
- Gaab, M.R.; Knoblich, O.E.; Fuhrmeister, U.; Pflughaupt, K.W.; Dietrich, K. Comparison of the Effects of Surgical Decompression and Resection of Local Edema in the Therapy of Experimental Brain Trauma: Investigation of ICP, EEG and Cerebral Metabolism in Cats. Pediatr. Neurosurg. 1979, 5, 484–498. [Google Scholar] [CrossRef]
- Armistead, F.J.; Gala De Pablo, J.; Gadêlha, H.; Peyman, S.A.; Evans, S.D. Cells Under Stress: An Inertial-Shear Microfluidic Determination of Cell Behavior. Biophys. J. 2019, 116, 1127–1135. [Google Scholar] [CrossRef] [Green Version]
- Nilsson, C.; Stahlberg, F.; Thomsen, C.; Henriksen, O.; Herning, M.; Owman, C. Circadian Variation in Human Cerebrospinal Fluid Production Measured by Magnetic Resonance Imaging. Am. J. Physiol.-Regul. Integr. Comp. Physiol. 2017, 262, R20–R24. [Google Scholar] [CrossRef]
- Battal, B.; Kocaoglu, M.; Bulakbasi, N.; Husmen, G.; Tuba Sanal, H.; Tayfun, C. Cerebrospinal Fluid Flow Imaging by Using Phase-Contrast MR Technique. Br. J. Radiol. 2011, 84, 758–765. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brinker, T.; Stopa, E.; Morrison, J.; Klinge, P. A New Look at Cerebrospinal Fluid Movement. Fluids Barriers CNS 2014, 11, 10. [Google Scholar] [CrossRef] [Green Version]
- Li, M.; Ransohoff, R.M. Multiple Roles of Chemokine CXCL12 in the Central Nervous System: A Migration from Immunology to Neurobiology. Prog. Neurobiol. 2008, 84, 116–131. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Giordano, F.A.; Link, B.; Glas, M.; Herrlinger, U.; Wenz, F.; Umansky, V.; Brown, J.M.; Herskind, C. Targeting the Post-Irradiation Tumor Microenvironment in Glioblastoma via Inhibition of CXCL12. Cancers 2019, 11, 272. [Google Scholar] [CrossRef] [Green Version]
- Behnan, J.; Finocchiaro, G.; Hanna, G. The Landscape of the Mesenchymal Signature in Brain Tumours. Brain 2019, 142, 847–866. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sottoriva, A.; Spiteri, I.; Piccirillo, S.G.M.; Touloumis, A.; Collins, V.P.; Marioni, J.C.; Curtis, C.; Watts, C.; Tavaré, S. Intratumor Heterogeneity in Human Glioblastoma Reflects Cancer Evolutionary Dynamics. Proc. Natl. Acad. Sci. USA 2013, 110, 4009–4014. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yamahira, S.; Satoh, T.; Yanagawa, F.; Tamura, M.; Takagi, T.; Nakatani, E.; Kusama, Y.; Sumaru, K.; Sugiura, S.; Kanamori, T. Stepwise Construction of Dynamic Microscale Concentration Gradients around Hydrogel-Encapsulated Cells in a Microfluidic Perfusion Culture Device. R. Soc. Open Sci. 2020, 7, 200027. [Google Scholar] [CrossRef] [PubMed]
- Tweedy, L.; Insall, R.H. Self-Generated Gradients Yield Exceptionally Robust Steering Cues. Front. Cell Dev. Biol. 2020, 8, 133. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shi, Y.; Riese, D.J.; Shen, J. The Role of the CXCL12/CXCR4/CXCR7 Chemokine Axis in Cancer. Front. Pharmacol. 2020, 11, 1969. [Google Scholar] [CrossRef] [PubMed]
- Seeger, F.H.; Rasper, T.; Fischer, A.; Muhly-Reinholz, M.; Hergenreider, E.; Leistner, D.M.; Sommer, K.; Manavski, Y.; Henschler, R.; Chavakis, E.; et al. Heparin Disrupts the CXCR4/SDF-1 Axis and Impairs the Functional Capacity of Bone Marrow–Derived Mononuclear Cells Used for Cardiovascular Repair. Circ. Res. 2012, 111, 854–862. [Google Scholar] [CrossRef] [Green Version]
- Zhou, Z.-H.; Karnaukhova, E.; Rajabi, M.; Reeder, K.; Chen, T.; Dhawan, S.; Kozlowski, S. Oversulfated Chondroitin Sulfate Binds to Chemokines and Inhibits Stromal Cell-Derived Factor-1 Mediated Signaling in Activated T Cells. PLoS ONE 2014, 9, e94402. [Google Scholar] [CrossRef]
Parameter | Variable | Value | Unit | Source |
---|---|---|---|---|
Density of fluid | ρ | 1 | g/mL | Anne Lui, Can J Anaesth, 1998 [39] |
Dynamic viscosity of fluid | µ | 0.7–1 | mPa·s | Bloomfield, Pediatr Neurosurg, 1998 [40] |
Temperature | T | 310.15 | K | Physiological temp |
Inlet velocity | v | 0.1–100 | µm/s | Munson JM, Can Man and Res, 2014 [7] |
Porosity | ε | 0.3 | Linninger A, IEEE Trans. on Biomed. Eng. 2007 [41] | |
Permeability | κ | 1.00 × 10−11 | cm2 | Munson JM, Cancer Research 2013 [18] |
Diffusion coefficient, chemokine | D_cxcl12 | 120 | µm2/s | Fleury M, Biophysics Journal, 2006 [34] |
Diffusion coefficient, protease | D_protease | 80 | µm2/s | Fleury M, Biophysics Journal, 2006 [34] |
Mass transfer coefficient, chemokine | k_cxcl12 | 2.80 × 10−5 | m/s | Calculated Value |
Mass transfer coefficient, protease | k_protease | 1.60 × 10−5 | m/s | Calculated Value |
Bulk concentration, chemokine | bulk_cxcl12 | 100 | nM | Estimated Value |
Bulk concentration, protease | bulk_protease | 1 | nM | Estimated Value |
Heparan sulfate concentration | HS | 2.60 × 10−3 | mM | Estimated Value |
Radius of sphere | r | 5.00 × 10−6 | M | Approximate Cell Diameter |
Chemokine binding rate | k_on | 9.30 × 104 | 1/(M·s) | Munson JM, Cancer Research 2013 [18] |
Chemokine unbinding rate | k_off | 1.16 × 10−5 | 1/s | Munson JM, Cancer Research 2013 [18] |
Chemokine release rate from protease | k_rel | 1.00 × 104 | 1/(M·s) | Estimated Value |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Stine, C.A.; Munson, J.M. Autologous Gradient Formation under Differential Interstitial Fluid Flow Environments. Biophysica 2022, 2, 16-33. https://doi.org/10.3390/biophysica2010003
Stine CA, Munson JM. Autologous Gradient Formation under Differential Interstitial Fluid Flow Environments. Biophysica. 2022; 2(1):16-33. https://doi.org/10.3390/biophysica2010003
Chicago/Turabian StyleStine, Caleb A., and Jennifer M. Munson. 2022. "Autologous Gradient Formation under Differential Interstitial Fluid Flow Environments" Biophysica 2, no. 1: 16-33. https://doi.org/10.3390/biophysica2010003