Too-few proteins prompt nanoparticles to clump

January 28, 2016
Rice University researchers observed nanoparticle aggregation induced by low concentrations of unfolded serum albumin proteins. They believe the proteins unfold upon binding to gold nanoparticles and prevent other proteins from joining them to form a protective casing around the particle. Credit: Rice University

Blood serum proteins have been observed combining one-to-one with gold nanoparticles and prompting them to aggregate, scientists at Rice University reported.

This is unexpected, according to Rice researchers Stephan Link and Christy Landes, who have led studies of the proteins most responsible for keeping solids in blood separated. In low concentrations, they said, the proteins irreversibly attach, unfold and then bring nanoparticles together.

This is counter to the purpose of albumin proteins, the most abundant in the blood stream, they said.

The paper, published this month in the American Chemical Society journal ACS Nano, has implications for diseases caused by aggregation, like Alzheimer's, and for nanoparticle toxicity issues, the researchers said. Gold nanoparticles are increasingly being used as therapeutic agents.

Several years ago the Rice team found that higher concentrations of (BSA), a near-match for its human counterpart, could keep naturally hydrophobic from clumping. In new experiments, some using technology that has only become available in recent years, BSA proteins in low concentrations were observed to unfold in the presence of gold nanoparticles.

This is a super-resolution map of identified individual bovine serum albumin molecules, as marked by the colored outlines. The gold nanowire, in gray and thousands of nanometers long, shows the relative size of the proteins, which occupy areas much larger than expected based on the size of their unfolded geometry. The researchers said this supports the finding that there's only space for one protein on the smaller nanoparticles studied. Credit: Rice University

"We think the protein is attaching first and unfolding, and that prevents other proteins from coming in," Link said. "But it also facilitates the aggregation."

"This is the most common protein in blood serum," Landes said. "Its job is to surround and make a nice hard shell around anything in solution that would otherwise be insoluble and stabilize the complicated mixture of cells, proteins and hormones in blood.

"What's important is the protein's ability to successfully coat otherwise hydrophobic steroid hormones, nanoparticles, viruses, anything," she said. "But in order for it to make that coating, it needs to stay nicely folded."

By unfolding in the presence of gold nanoparticles, they said, the protein does two things: It spreads out on the particle, leaving no room for other proteins to attach, and exposes its usually hidden hydrophobic core, which encourages aggregation with other protein-nanoparticle sets.

"This is an issue whether people use nanoparticles for therapeutic purposes or just come into contact with nanoparticles in products or the environment," Landes said. "If serum albumin can do its job, everything's fine. But we can't help but notice that protein unfolding, protein aggregation and fibril formation are at the root of all sorts of diseases."

While their previous research showed albumin proteins in high concentrations keep nanoparticles soluble, "there are biological situations where the concentration of serum albumin protein could be low enough to cause problems," Landes said.

They also noted that two other blood-borne proteins, fibrinogen and globulin, cause nanoparticles to aggregate regardless of their concentrations. "They unfold no matter what the concentration, meaning that the BSA or human are really designed to make this coating and keep everything from running out of control," Link said.

"We're saying people really need to pay attention to the ratio between the —in this case, BSA—and nanoparticles, because different things can happen."

Explore further: Bovine blood keeps gold nanoparticles stable

More information: Sergio Dominguez-Medina et al. Adsorption and Unfolding of a Single Protein Triggers Nanoparticle Aggregation, ACS Nano (2016). DOI: 10.1021/acsnano.5b06439

Related Stories

Bovine blood keeps gold nanoparticles stable

May 14, 2013

( —A protein from cow blood has the remarkable ability to keep gold nanoparticles from clumping in a solution. The discovery could lead to improved biomedical applications and contribute to projects that use nanoparticles ...

The case of the sticky protein

December 18, 2015

Proteins are like a body's in-house Lego set. These large, complex molecules are made up of building blocks called amino acids. Most of the time, proteins fold correctly, but sometimes they can misfold. This misfolding causes ...

Observing nano-bio interactions in real time

September 15, 2015

Researchers at the National University of Singapore (NUS) have developed a technique to observe, in real time, how individual blood components interact and modify advanced nanoparticle therapeutics. The method, developed ...

Recommended for you

Nano-decoy lures human influenza A virus to its doom

October 25, 2016

To infect its victims, influenza A heads for the lungs, where it latches onto sialic acid on the surface of cells. So researchers created the perfect decoy: A carefully constructed spherical nanoparticle coated in sialic ...

New method increases energy density in lithium batteries

October 24, 2016

Yuan Yang, assistant professor of materials science and engineering at Columbia Engineering, has developed a new method to increase the energy density of lithium (Li-ion) batteries. He has built a trilayer structure that ...

Nanofiber coating prevents infections of prosthetic joints

October 24, 2016

In a proof-of-concept study with mice, scientists at The Johns Hopkins University show that a novel coating they made with antibiotic-releasing nanofibers has the potential to better prevent at least some serious bacterial ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.