News | Can neutral molecules behave as charged? US team challenges conventional biochemistry
A University of Massachusetts Amherst-led study challenges a longstanding view of polyzwitterions: although considered electrically neutral, they move through an electric field like charged particles. Published in Nature Communications, the work may support analysis of proteins and carbohydrates, drug delivery and other biomedical applications.
The study was conducted by polymer science and engineering graduate student Yeseul Lee and senior author Murugappan Muthukumar, Wilmer D. Barrett Professor.
Neutral polymers behave as if charged, overturning a standard assumption
Polyzwitterions consist of zwitterionic units containing both positive and negative groups but are neutral overall, so conventionally they should not move in an electric field. Single-molecule electrophoresis showed that:
PSBMA behaves as if negatively charged
PMPC behaves as if positively charged
In other words, neutral molecules expected to show no response moved in a particular direction.
"My research examines the behavior of proteins and amino acids, the building blocks of biological polymers," Lee said. "In the crowded cellular environment, understanding how molecules move and communicate is essential."
Why do neutral molecules move? The key is "hidden charge"
The team identified the mechanism:
A polyzwitterion is structured like a rib, with one charged end projecting outward and the other near the polymer backbone. The study showed:
PSBMA has a negative charge at the rib's "tip"
PMPC has a positive charge at the "tip"
The other charge is weakened and largely "hidden" near the backbone
The charge at the tip therefore determines the direction of movement in an electric field.
A second breakthrough: electric fields within cells are not uniform
Scientists generally assumed that the cellular electrolyte around biomacromolecules has a uniform dielectric constant, weakening each charge equally. The study instead found:
Local dielectric constants differ around positive and negative charges
The dielectric constant is substantially lower near the polymer backbone
It increases farther from the backbone and closer to the tip
This suggests microscopic electric fields inside cells are more complex than previously thought and molecular interactions cannot be described by one uniform rule.
"This contributes to the fundamental mechanics of biochemistry," Muthukumar said. "No one knew the dielectric constant changed with distance from the polymer backbone. We observed it and quantified the consequences."
A new foundation for protein research and precision medicine
The finding that neutral molecules can behave as charged provides a new perspective on protein assembly, movement and interactions. The team said it may advance:
Early disease detection
Precision drug delivery
Protein and carbohydrate analysis and identification
Biomolecule screening and separation
The study was funded by the US National Science Foundation (NSF) and Air Force Office of Scientific Research (AFOSR).
News | Can neutral molecules behave as charged? US team challenges conventional biochemistry
News | Can neutral molecules behave as charged? US team challenges conventional biochemistry
A University of Massachusetts Amherst-led study challenges a longstanding view of polyzwitterions: although considered electrically neutral, they move through an electric field like charged particles. Published in Nature Communications, the work may support analysis of proteins and carbohydrates, drug delivery and other biomedical applications.
The study was conducted by polymer science and engineering graduate student Yeseul Lee and senior author Murugappan Muthukumar, Wilmer D. Barrett Professor.
Neutral polymers behave as if charged, overturning a standard assumption
Polyzwitterions consist of zwitterionic units containing both positive and negative groups but are neutral overall, so conventionally they should not move in an electric field. Single-molecule electrophoresis showed that:
PSBMA behaves as if negatively charged
PMPC behaves as if positively charged
In other words, neutral molecules expected to show no response moved in a particular direction.
"My research examines the behavior of proteins and amino acids, the building blocks of biological polymers," Lee said. "In the crowded cellular environment, understanding how molecules move and communicate is essential."
Why do neutral molecules move? The key is "hidden charge"
The team identified the mechanism:
A polyzwitterion is structured like a rib, with one charged end projecting outward and the other near the polymer backbone. The study showed:
PSBMA has a negative charge at the rib's "tip"
PMPC has a positive charge at the "tip"
The other charge is weakened and largely "hidden" near the backbone
The charge at the tip therefore determines the direction of movement in an electric field.
A second breakthrough: electric fields within cells are not uniform
Scientists generally assumed that the cellular electrolyte around biomacromolecules has a uniform dielectric constant, weakening each charge equally. The study instead found:
Local dielectric constants differ around positive and negative charges
The dielectric constant is substantially lower near the polymer backbone
It increases farther from the backbone and closer to the tip
This suggests microscopic electric fields inside cells are more complex than previously thought and molecular interactions cannot be described by one uniform rule.
"This contributes to the fundamental mechanics of biochemistry," Muthukumar said. "No one knew the dielectric constant changed with distance from the polymer backbone. We observed it and quantified the consequences."
A new foundation for protein research and precision medicine
The finding that neutral molecules can behave as charged provides a new perspective on protein assembly, movement and interactions. The team said it may advance:
Early disease detection
Precision drug delivery
Protein and carbohydrate analysis and identification
Biomolecule screening and separation
The study was funded by the US National Science Foundation (NSF) and Air Force Office of Scientific Research (AFOSR).
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