Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions
Diffusive transport of macromolecules and nanoparticles in charged fibrous media is of interest in many biological applications, including drug delivery and separation processes. Experimental findings have shown that diffusion can be significantly hindered by electrostatic interactions between the d...
| Main Authors: | , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Elsevier
2015
|
| Online Access: | http://hdl.handle.net/1721.1/96065 https://orcid.org/0000-0003-2220-4365 |
| _version_ | 1826206374592249856 |
|---|---|
| author | Stylianopoulos, Triantafyllos Poh, Ming-Zher Insin, Numpon Bawendi, Moungi G. Fukumura, Dai Munn, Lance L. Jain, Rakesh K. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Stylianopoulos, Triantafyllos Poh, Ming-Zher Insin, Numpon Bawendi, Moungi G. Fukumura, Dai Munn, Lance L. Jain, Rakesh K. |
| author_sort | Stylianopoulos, Triantafyllos |
| collection | MIT |
| description | Diffusive transport of macromolecules and nanoparticles in charged fibrous media is of interest in many biological applications, including drug delivery and separation processes. Experimental findings have shown that diffusion can be significantly hindered by electrostatic interactions between the diffusing particle and charged components of the extracellular matrix. The implications, however, have not been analyzed rigorously. Here, we present a mathematical framework to study the effect of charge on the diffusive transport of macromolecules and nanoparticles in the extracellular matrix of biological tissues. The model takes into account steric, hydrodynamic, and electrostatic interactions. We show that when the fiber size is comparable to the Debye length, electrostatic forces between the fibers and the particles result in slowed diffusion. However, as the fiber diameter increases the repulsive forces become less important. Our results explain the experimental observations that neutral particles diffuse faster than charged particles. Taken together, we conclude that optimal particles for delivery to tumors should be initially cationic to target the tumor vessels and then change to neutral charge after exiting the blood vessels. |
| first_indexed | 2024-09-23T13:28:52Z |
| format | Article |
| id | mit-1721.1/96065 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:28:52Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/960652022-10-01T15:29:17Z Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions Stylianopoulos, Triantafyllos Poh, Ming-Zher Insin, Numpon Bawendi, Moungi G. Fukumura, Dai Munn, Lance L. Jain, Rakesh K. Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Chemistry Bawendi, Moungi G. Insin, Numpon Jain, Rakesh K. Diffusive transport of macromolecules and nanoparticles in charged fibrous media is of interest in many biological applications, including drug delivery and separation processes. Experimental findings have shown that diffusion can be significantly hindered by electrostatic interactions between the diffusing particle and charged components of the extracellular matrix. The implications, however, have not been analyzed rigorously. Here, we present a mathematical framework to study the effect of charge on the diffusive transport of macromolecules and nanoparticles in the extracellular matrix of biological tissues. The model takes into account steric, hydrodynamic, and electrostatic interactions. We show that when the fiber size is comparable to the Debye length, electrostatic forces between the fibers and the particles result in slowed diffusion. However, as the fiber diameter increases the repulsive forces become less important. Our results explain the experimental observations that neutral particles diffuse faster than charged particles. Taken together, we conclude that optimal particles for delivery to tumors should be initially cationic to target the tumor vessels and then change to neutral charge after exiting the blood vessels. National Institutes of Health (U.S.) (5PO1CA080124) National Institutes of Health (U.S.) (RO1CA126642) 2015-03-17T20:46:46Z 2015-03-17T20:46:46Z 2010-09 2010-02 Article http://purl.org/eprint/type/JournalArticle 00063495 1542-0086 http://hdl.handle.net/1721.1/96065 Stylianopoulos, Triantafyllos, Ming-Zher Poh, Numpon Insin, Moungi G. Bawendi, Dai Fukumura, Lance L. Munn, and Rakesh K. Jain. “Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions.” Biophysical Journal 99, no. 5 (September 2010): 1342–1349. © 2010 Biophysical Society. https://orcid.org/0000-0003-2220-4365 en_US http://dx.doi.org/10.1016/j.bpj.2010.06.016 Biophysical Journal Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | Stylianopoulos, Triantafyllos Poh, Ming-Zher Insin, Numpon Bawendi, Moungi G. Fukumura, Dai Munn, Lance L. Jain, Rakesh K. Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions |
| title | Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions |
| title_full | Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions |
| title_fullStr | Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions |
| title_full_unstemmed | Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions |
| title_short | Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions |
| title_sort | diffusion of particles in the extracellular matrix the effect of repulsive electrostatic interactions |
| url | http://hdl.handle.net/1721.1/96065 https://orcid.org/0000-0003-2220-4365 |
| work_keys_str_mv | AT stylianopoulostriantafyllos diffusionofparticlesintheextracellularmatrixtheeffectofrepulsiveelectrostaticinteractions AT pohmingzher diffusionofparticlesintheextracellularmatrixtheeffectofrepulsiveelectrostaticinteractions AT insinnumpon diffusionofparticlesintheextracellularmatrixtheeffectofrepulsiveelectrostaticinteractions AT bawendimoungig diffusionofparticlesintheextracellularmatrixtheeffectofrepulsiveelectrostaticinteractions AT fukumuradai diffusionofparticlesintheextracellularmatrixtheeffectofrepulsiveelectrostaticinteractions AT munnlancel diffusionofparticlesintheextracellularmatrixtheeffectofrepulsiveelectrostaticinteractions AT jainrakeshk diffusionofparticlesintheextracellularmatrixtheeffectofrepulsiveelectrostaticinteractions |