# Development of a Novel Technology for Preparative Fractionation and Characterization of Lipoprotein Particles

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $333,340

## Abstract

Project Summary
High-density lipoproteins (HDL) are the single strongest predictors of longevity and protect against a wide array
of diseases, from chronic conditions like cardiovascular disease and neurodegeneration, to acute infection and
sepsis mortality, and everything in between. If we can get HDL right, we can live long, healthy lives. Yet despite
over 50 years of research, HDL have remained an enigma and therapeutic approaches for improving HDL
function have proven elusive. HDL are highly heterogeneous and difficult to isolate and characterize because of
their colloidal, multi-molecular nature yet very small size (< 20 nm in diameter). A critical barrier to progress is
the lack of technologies to simultaneously quantify the size and number of HDL particles, and isolate them such
that they remain intact and amenable for a variety of both compositional and functional analyses. The objectives
of this project are to gain new technological knowledge on the application of our instrument using size exclusion
chromatography coupled with multiple inline static and dynamic optical detectors, and to measure the
quantitative advantages of this technology over state-of-the-art approaches for the isolation and physicochemical
characterization of HDL particles. In particular, this project will solve the critical problem of quantifying the number
of particles using a non-destructive approach that simultaneously measures and fractionates the particles by
size, making it possible to evaluate the function and composition of different size-based HDL subclasses on a
per particle basis. Currently, researchers are limited by the simple problem of not having a good denominator:
the only option is to express the amount of an important constituent or functional capacity in the HDL we have
measured based on a rough substitute for “concentration” (e.g. total protein in the isolated fraction). Therefore,
if there is more of a certain protein (or higher functional capacity) in sample A vs. B, there is no way to distinguish
whether that is simply because sample A has more particles in it or whether there are more molecules of that
protein (or higher functional capacity) per particle. Different sizes of HDL carry different absolute and relative
amounts of individual proteins, lipids, and other components, from as few as 2 molecules of the main
apolipoprotein, apolipoprotein A-I, and 12 molecules of cholesteryl ester in the smallest HDL, to as many as 4-6
molecules of apolipoprotein A-I and hundreds of molecules of cholesteryl ester, with similar variability in the
concentrations of other critical components that confer dozens of functions, from antioxidant, to
immunomodulatory, to anti-proteolytic to name a few. And because particle size determines binding affinity to
receptors, clearance rates, and likely even whether HDL can cross the blood-brain-barrier, knowing the number
of particles of different sizes, and also the per particle composition of the cargo they carry i...

## Key facts

- **NIH application ID:** 10503961
- **Project number:** 1R01GM147545-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Angela M Zivkovic
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $333,340
- **Award type:** 1
- **Project period:** 2022-09-25 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10503961

## Citation

> US National Institutes of Health, RePORTER application 10503961, Development of a Novel Technology for Preparative Fractionation and Characterization of Lipoprotein Particles (1R01GM147545-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10503961. Licensed CC0.

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