# Regulation and modeling of transport across tissue barriers

> **NIH NIH R35** · UNIV OF MARYLAND, COLLEGE PARK · 2024 · $21,565

## Abstract

Project Summary
Physiological transport of fluid, molecules, proteins, and cells throughout the body is critical for homeostasis.
While transport processes like cell migration and molecular passage across cellular barriers are well
documented, less is known about transport across the interstitial tissue spaces and into lymphatic vessels.
Lymphatic vessels are critical for maintenance of tissue homeostasis and forming the adaptive immune
response, as they are the natural conduit between peripheral tissues and the lymph nodes (LNs), where the
immune response is shaped. Because particulates are primarily shuttled via lymphatic vessels, lymphatics have
received considerable attention in recent years as potential targets for drug delivery, particularly for immune
modulation. Transport across interstitial tissue governs what enters lymphatic vessels vs. blood vessels and thus
understanding extracellular tissues is vital to design therapeutics. However, we do not yet fully understand how
physiological processes and conditions such as interstitial flow or inflammation affect transport across interstitial
tissue spaces and into lymphatics. My research program will answer two key questions: 1) How do
physiological processes affect 1) lymphatic transport and its regulation, and 2) transport across
extracellular tissue? To address the first question, we propose to develop physiologically relevant in vitro model
systems that can recapitulate conditions within peripheral tissues and nanoparticle tools that both allow probing
how specific mechanisms, including fluid flow and inflammation, modulate lymphatic transport specifically.
Results from these studies will provide new insights into regulation of lymphatic transport, new model systems
for studying lymphatic transport, and new design criteria to maximize targeting lymphatic transport for therapeutic
purposes. To address the second question, we will combine two techniques: multiple particle tracking (MPT) and
live ex vivo tissue slice cultures. MPT uses nanoparticle diffusion over time to extract information about tissue
mesh spacing or microrheology and provides a medium for studying physiological processes like flow. Live tissue
slice cultures maintain tissue structure ex vivo and allow for real-time assessment of interstitial tissue structures.
Results from combining these techniques will provide a better understanding of how physiological processes
affect extracellular spaces and provide insights into design criteria for therapeutics to cross extracellular tissue
barriers. In summary, the proposed work will advance our knowledge about physiological processes governing
lymphatic transport and its regulation, and also shed light into how processes like inflammation, interstitial flow,
and edema affect extracellular tissue spaces. Ultimately, the vision for my lab’s research is to design crucial
scientific methods to be used by the broader community, identify design criteria and computational
models to pred...

## Key facts

- **NIH application ID:** 11090261
- **Project number:** 3R35GM142835-04S1
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Katharina Maisel
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $21,565
- **Award type:** 3
- **Project period:** 2021-07-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11090261

## Citation

> US National Institutes of Health, RePORTER application 11090261, Regulation and modeling of transport across tissue barriers (3R35GM142835-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11090261. Licensed CC0.

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