Malaria parasite's cell-entry structure imaged in atomic detail

Cryo-electron microscopy reveals how Plasmodium creates temporary gaps in red blood cell membranes, opening avenues for new treatments.

By LineZotpaper

Published23 October 2026

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For the first time, researchers have imaged the precise molecular structure that malaria parasites use to invade human red blood cells. A team led by Chi-Min Ho at Columbia University captured the moving junction, a ring-shaped portal that opens and closes in less than a minute, in atomic detail using cryo-electron microscopy. The findings, published in a new study, explain how the parasite remodels the host cell's membrane to slip through without a trace, potentially informing the next generation of malaria drugs.

Malaria, caused by the Plasmodium parasite, kills approximately 600,000 people each year. The parasite invades red blood cells to proliferate, but the exact mechanism of entry has remained elusive because the process is so rapid and tiny.

Chi-Min Ho, a microbiologist and structural biologist at Columbia University, and her team used cryo-electron microscopy to probe the four individual protein units that make up each anchor in the moving junction. They found that the parasite injects three proteins into the red blood cell, forming a dense wedge beneath the membrane surface. A fourth protein connects this structure to the invader. The proteins produce electrostatic forces and pressure that crowd and displace lipid molecules, deforming the membrane and reversing its curvature. This allows the parasite to push through, with some lipids even reassembling into a protective membrane around the invader, before the cell seals behind it.

"It's a totally mind-blowing paper," said Jake Baum, a parasitologist at the University of New South Wales who was not involved in the research. "At the end of the day, this is not molecular biology. This is biophysics."

The research builds on decades of work, from early electron microscopy in the 1970s to today's advanced imaging. "Because of that, we didn't really know anything about how it works," Ho said of the moving junction.

The study's detailed model could help guide drug discovery not only for malaria but also for other parasitic diseases like cyclosporiasis and toxoplasmosis, which use similar invasion strategies. Kirk Deitsch, a microbiologist and immunologist at Weill Cornell Medicine, noted that "the food supply happens to be our red blood cells. That's why they're invading us."

Analysis

Why This Matters

The discovery provides a clear molecular target for developing drugs that block the moving junction, potentially reducing malaria's annual death toll of 600,000.
Understanding how Plasmodium remodels cell membranes without rupturing them could inspire new approaches in drug delivery or cell biology.
The same invasion mechanism is shared by related parasites, making this finding broadly relevant for treating toxoplasmosis and cyclosporiasis.

Background

Malaria has afflicted humans for centuries, but the Plasmodium parasite was only identified in 1880 by Charles Louis Alphonse Laveran. The parasite invades red blood cells as merozoites, using a ring of protein anchors called the moving junction to create a temporary portal. Imaging this structure has been extremely challenging because it opens and closes in under a minute and is smaller than the red blood cell itself, which is about 8 micrometers across. Until now, only the broad outlines of the process were known.

Key Perspectives

Chi-Min Ho (Columbia University): Her team's cryo-electron microscopy work has now resolved the four-protein complex of the moving junction, showing how electrostatic forces and lipid displacement let the parasite slip through without leaving a hole. Jake Baum (University of New South Wales): The parasitologist described the paper as "mind-blowing" and noted it represents a shift from molecular biology to biophysics in understanding the invasion. Kirk Deitsch (Weill Cornell Medicine): He contextualised the invasion as the parasite using human red blood cells as a food supply during its life cycle in the mosquito.

What to Watch

Whether pharmaceutical companies pursue the moving junction proteins as drug targets in preclinical trials.
Further structural studies on related parasites such as Toxoplasma to see if the same model applies.
Advances in cryo-electron microscopy that could allow real-time imaging of the invasion process.

Sources

Malaria Parasite Caught in the Act of Breaking and Entering · Quanta Magazine

Checked

11 claims in this story checked against 1 source: 9 supported.

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Partly supportedThe malaria parasite’s cell-entry structure was imaged in atomic detail.Quanta Magazine: “Now, Ho’s lab has imaged the moving junction right at the moment of invasion, in unprecedented detail.”
Partly supportedFor the first time, researchers imaged the precise molecular structure malaria parasites use to invade red blood cells.Quanta Magazine: “It opens and closes so rapidly, at such a small scale, that imaging technologies couldn’t capture it. Researchers had no clue what the portal structure actually looked like. “Because of that,” said Chi-Min Ho, a microbiologist and structural biologist at Columbia University, “we didn’t really know anything about how it works.” Now, Ho’s lab has imaged the moving junction right at the moment of invasion, in unprecedented detail.”
SupportedCryo-electron microscopy revealed how Plasmodium creates temporary gaps in red blood cell membranes, opening avenues for new treatments.Quanta Magazine: “To get in, the microbe creates a ring-shaped structure called the moving junction, which briefly creates a gap in the cell membrane it can slip through. The gap then disappears without a trace.”
SupportedThe moving junction is a ring-shaped portal that opens and closes in less than a minute.Quanta Magazine: “The moving junction forms a continuous portal in the host cell membrane for the parasite to travel through. Once the parasite is fully inside, the cell membrane seals up behind it. The whole process takes less than a minute.”
SupportedChi-Min Ho’s team used cryo-electron microscopy to examine four protein units in each anchor of the moving junction.Quanta Magazine: “Ho and the other authors of the new paper used cryo-electron microscopy to probe the four individual protein units in each anchor.”
SupportedThe parasite injects three proteins into the red blood cell to form a dense wedge beneath the membrane, while a fourth protein connects it to the invader.Quanta Magazine: “The parasite injects into the red blood cell three proteins, which form a dense wedge beneath the membrane surface; a fourth protein connects this structure to the invader.”
SupportedThe proteins’ electrostatic forces and pressure crowd and displace lipids, deforming the membrane and reversing its curvature.Quanta Magazine: “The proteins produce electrostatic forces and pressure in the cell membrane, which crowd and displace its lipid molecules. This deforms the membrane and reverses its curvature.”
SupportedSome lipids reassemble into a protective membrane around the parasite before the cell seals behind it.Quanta Magazine: “some lipids slough off and reassemble into a protective membrane for the invader — before re-forming and sealing behind it.”
SupportedMalaria kills approximately 600,000 people each year.Quanta Magazine: “it still kills approximately 600,000 people each year.”
SupportedJake Baum called the paper “totally mind-blowing” and said, “At the end of the day, this is not molecular biology. This is biophysics.”Quanta Magazine: ““It’s a totally mind-blowing paper,” said Jake Baum, a parasitologist at the University of New South Wales, who was not involved in the research. “At the end of the day, this is not molecular biology. This is biophysics.””
SupportedKirk Deitsch said, “the food supply happens to be our red blood cells. That's why they're invading us.”Quanta Magazine: ““The food supply happens to be our red blood cells,” said Kirk Deitsch, a microbiologist and immunologist at Weill Cornell Medicine in New York. “That’s why they’re invading us.””