Spatial Configurations of 3D Extracellular Matrix Collagen Density and Anisotropy Simultaneously Guide Angiogenesis.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238922 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7358 (Electronic) Linking ISSN: 1553734X NLM ISO Abbreviation: PLoS Comput Biol Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, [2005]-

Collagen*/chemistry ; Extracellular Matrix*; Anisotropy ; Morphogenesis ; Cell Communication

Extracellular matrix (ECM) collagen density and fibril anisotropy are thought to affect the development of new vasculatures during pathologic and homeostatic angiogenesis. Computational simulation is emerging as a tool to investigate the role of matrix structural configurations on cell guidance. However, prior computational models have only considered the orientation of collagen as a model input. Recent experimental evidence indicates that cell guidance is simultaneously influenced by the direction and intensity of alignment (i.e., degree of anisotropy) as well as the local collagen density. The objective of this study was to explore the role of ECM collagen anisotropy and density during sprouting angiogenesis through simulation in the AngioFE and FEBio modeling frameworks. AngioFE is a plugin for FEBio (Finite Elements for Biomechanics) that simulates cell-matrix interactions during sprouting angiogenesis. We extended AngioFE to represent ECM collagen as deformable 3D ellipsoidal fibril distributions (EFDs). The rate and direction of microvessel growth were modified to depend simultaneously on the ECM collagen anisotropy (orientation and degree of anisotropy) and density. The sensitivity of growing neovessels to these stimuli was adjusted so that AngioFE could reproduce the growth and guidance observed in experiments where microvessels were cultured in collagen gels of varying anisotropy and density. We then compared outcomes from simulations using EFDs to simulations that used AngioFE's prior vector field representation of collagen anisotropy. We found that EFD simulations were more accurate than vector field simulations in predicting experimentally observed microvessel guidance. Predictive simulations demonstrated the ability of anisotropy gradients to recruit microvessels across short and long distances relevant to wound healing. Further, simulations predicted that collagen alignment could enable microvessels to overcome dense tissue interfaces such as tumor-associated collagen structures (TACS) found in desmoplasia and tumor-stroma interfaces. This approach can be generalized to other mechanobiological relationships during cell guidance phenomena in computational settings.
Competing Interests: The authors have no competing interests to declare.
(Copyright: © 2023 LaBelle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In Silico Cell Tissue Sci. 2015 Dec 18;2:1. (PMID: 26709368)
Angiogenesis. 2015 Jul;18(3):219-32. (PMID: 25795217)
Arthritis Rheum. 2007 Jan;56(1):224-33. (PMID: 17195226)
Front Cell Dev Biol. 2021 May 10;9:659654. (PMID: 34041240)
Acta Biomater. 2021 Nov;135:368-382. (PMID: 34390846)
Arthritis Rheum. 2007 Aug;56(8):2482-91. (PMID: 17665450)
Front Physiol. 2020 Aug 14;11:1026. (PMID: 33013445)
Croat Med J. 2021 Feb 28;62(1):59-67. (PMID: 33660962)
Biomech Model Mechanobiol. 2016 Oct;15(5):1079-90. (PMID: 26564173)
J Vasc Res. 2012;49(3):185-97. (PMID: 22433458)
J Orthop Res. 1994 Mar;12(2):238-45. (PMID: 8164097)
J Anat. 2001 Nov;199(Pt 5):503-26. (PMID: 11760883)
J Biomech. 2006;39(10):1842-51. (PMID: 16024026)
Wiley Interdiscip Rev Syst Biol Med. 2015 Jul-Aug;7(4):183-94. (PMID: 25903383)
Nat Rev Rheumatol. 2021 Apr;17(4):195-212. (PMID: 33526927)
J Theor Biol. 1999 Aug 21;199(4):449-71. (PMID: 10441462)
Biophys J. 2018 Nov 6;115(9):1630-1637. (PMID: 30297132)
J Biomech Eng. 1997 May;119(2):137-45. (PMID: 9168388)
PLoS One. 2018 Jan 3;13(1):e0189668. (PMID: 29298298)
BMC Med. 2006 Dec 26;4(1):38. (PMID: 17190588)
Am J Physiol Heart Circ Physiol. 2014 Jul 15;307(2):H152-64. (PMID: 24816262)
Cancer Discov. 2012 Sep;2(9):772-4. (PMID: 22969116)
Mol Cancer. 2022 Nov 2;21(1):208. (PMID: 36324128)
Arthritis Res. 2002;4(4):252-60. (PMID: 12106496)
Biophys J. 2000 Jul;79(1):144-52. (PMID: 10866943)
In Vitro Cell Dev Biol Anim. 1996 Jul-Aug;32(7):409-19. (PMID: 8856341)
Int J Cancer. 1999 May 17;81(4):629-36. (PMID: 10225455)
Am J Physiol Heart Circ Physiol. 2007 Dec;293(6):H3650-8. (PMID: 17933969)
Sci Adv. 2020 Aug 21;6(34):. (PMID: 32937368)
Biomech Model Mechanobiol. 2020 Dec;19(6):2525-2551. (PMID: 32623543)
J Biomech Eng. 2012 Jan;134(1):011005. (PMID: 22482660)
Biomech Model Mechanobiol. 2015 Jan;14(1):1-13. (PMID: 24718853)
Magn Reson Med. 2004 Dec;52(6):1358-72. (PMID: 15562495)
Adv Wound Care (New Rochelle). 2015 Mar 1;4(3):119-136. (PMID: 25785236)
PLoS One. 2014 Jan 22;9(1):e85178. (PMID: 24465500)
Bull Math Biol. 2005 Mar;67(2):313-37. (PMID: 15710183)
ACS Biomater Sci Eng. 2018 Aug 13;4(8):2967-2976. (PMID: 33435017)
J R Soc Interface. 2010 Jan 6;7(42):19-34. (PMID: 19324672)
J Biomech Eng. 2009 Jun;131(6):061003. (PMID: 19449957)
Cancer Metab. 2020 Jul 2;8:14. (PMID: 32637098)
Am J Pathol. 2011 Mar;178(3):1221-32. (PMID: 21356373)
Mol Cancer Res. 2012 Nov;10(11):1403-18. (PMID: 23024188)
IEEE Trans Med Imaging. 2022 Feb;41(2):446-455. (PMID: 34559646)
Cardiovasc Res. 2008 May 1;78(2):324-32. (PMID: 18310100)
Biomech Model Mechanobiol. 2015 Aug;14(4):767-82. (PMID: 25429840)
Nature. 1967 Jan 21;213(5073):256-60. (PMID: 6030602)
Comput Methods Biomech Biomed Engin. 2013;16(7):790-801. (PMID: 22515707)
Ann Biomed Eng. 2015 Jul;43(7):1531-42. (PMID: 25994280)
Curr Opin Cell Biol. 2021 Oct;72:63-71. (PMID: 34186415)
Ann Rheum Dis. 2015 Jan;74(1):196-203. (PMID: 24095939)
Biophys J. 2014 Dec 2;107(11):2592-603. (PMID: 25468338)
Int J Mol Sci. 2021 Jun 25;22(13):. (PMID: 34202183)
J Biomech Eng. 1998 Oct;120(5):660-6. (PMID: 10412446)
PLoS Comput Biol. 2009 Jul;5(7):e1000445. (PMID: 19629173)
Wound Repair Regen. 2011 Mar-Apr;19(2):134-48. (PMID: 21362080)
Am J Physiol Heart Circ Physiol. 2022 May 1;322(5):H806-H818. (PMID: 35333118)
J Biomech. 2016 May 24;49(8):1388-1401. (PMID: 26805459)
J Anat. 1996 Feb;188 ( Pt 1):87-95. (PMID: 8655419)
Biophys J. 2014 Dec 2;107(11):2546-58. (PMID: 25468334)

R01 AR069297 United States AR NIAMS NIH HHS; R01 GM083925 United States GM NIGMS NIH HHS; R01 HL131856 United States HL NHLBI NIH HHS; U24 EB029007 United States EB NIBIB NIH HHS

9007-34-5 (Collagen)

Date Created: 20231023 Date Completed: 20231106 Latest Revision: 20240210

20240210

PMC10621972

10.1371/journal.pcbi.1011553

37871113