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Related Concept Videos

The Extracellular Matrix01:29

The Extracellular Matrix

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In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
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Proteins show rotational as well as lateral diffusion across the membrane. The lateral diffusion of proteins was confirmed through the cell fusion experiment where mouse and human cells were fused, resulting in hybrid cells. When the human and mouse cells fused, the specific membrane proteins on human and mouse cells were marked with the red and green-fluorescent markers, respectively. Initially, the red and green fluorescence was located on the respective hemisphere of the cell. As time...
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Drugs must traverse multiple biological barriers, such as multi-layered skin, single-layered intestinal epithelium, and the plasma membrane, to reach their target sites within the body. The plasma membrane, a highly structured composite of phospholipids, carbohydrates, and proteins, is the cell's protective boundary, facilitating selective substance exchange.
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Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. This extracellular matrix (ECM) is composed of fibrous proteins like collagen, elastin, and fibronectin in a ground substance consisting of interstitial fluid, cell adhesion proteins, and proteoglycans. The proteoglycans form a gel-like material in the spaces between cells and provide hydration, buffering, binding, and force...
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Upon entering the systemic circulation, drugs can distribute into the interstitial and intracellular fluid of various tissue cells. This distribution is facilitated by the binding of drugs to different cellular components within tissues, which may lead to drug accumulation in specific areas. Drugs bound to tissue components serve as reservoirs that release free drugs back into the system, prolonging the drug's overall action. However, this accumulation can also result in local toxicity.
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Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice
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The Extracellular Matrix Limits Nanoparticle Diffusion and Cellular Uptake in a Tissue-Specific Manner.

Devorah Cahn1,2, Alexa Stern1, Michael Buckenmeyer2

  • 1Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.

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Nanoparticle coatings impact drug delivery by affecting how nanoparticles move through the extracellular matrix (ECM). Low molecular weight PEG coatings balance penetration and cell uptake, but branched PEG enhances tissue-specific delivery.

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Area of Science:

  • Biomedical Engineering
  • Materials Science
  • Nanotechnology

Background:

  • Extracellular matrix (ECM) remodeling in diseases hinders nanoparticle drug delivery.
  • Understanding ECM barriers is crucial for effective nanoparticle design.

Purpose of the Study:

  • To investigate how tissue-specific ECM properties affect nanoparticle diffusion and cellular uptake.
  • To determine the influence of PEGylation on nanoparticle penetration through ECM barriers.

Main Methods:

  • Fluorescence video microscopy to assess nanoparticle diffusion in ECM.
  • Flow cytometry to measure cellular uptake of nanoparticles.
  • Evaluation of various PEGylation strategies (chain size, branching) on nanoparticle performance.

Main Results:

  • Purified collagen presented a significant barrier to nanoparticle diffusion compared to decellularized tissue ECM.
  • Dense PEG coatings increased nanoparticle diffusion rates by up to 2000-fold and cellular uptake by 5-fold.
  • Nanoparticle mobility varied by tissue type, and optimal PEGylation depended on ECM concentration.
  • Branched PEG coatings showed tissue-specific enhancements in ECM penetration and cellular uptake.

Conclusions:

  • Low molecular weight PEG coatings offer a balance between ECM penetration and cellular uptake.
  • Branched PEGylation can be optimized for tissue-specific nanoparticle delivery.
  • Insights into ECM barrier functions can guide the design of more effective nanoparticle therapeutics.