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The in vitro gastrointestinal digestion-associated protein corona of polystyrene nano- and microplastics increases their uptake by human THP-1-derived macrophages

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Hugo Brouwer, Hugo Brouwer, Hans Bouwmeester Hugo Brouwer, Hugo Brouwer, Hugo Brouwer, Mathias Busch, Mathias Busch, Mathias Busch, Hugo Brouwer, Mathias Busch, Mathias Busch, Mathias Busch, Hugo Brouwer, Hugo Brouwer, Mathias Busch, Hugo Brouwer, Hugo Brouwer, Hans Bouwmeester Hugo Brouwer, Mathias Busch, Hans Bouwmeester Hans Bouwmeester Hans Bouwmeester Hans Bouwmeester Mojtaba Porbahaie, Mojtaba Porbahaie, Hugo Brouwer, Sjef Boeren, Hans Bouwmeester Sjef Boeren, Sjef Boeren, Mathias Busch, Mathias Busch, Mathias Busch, Hans Bouwmeester Hans Bouwmeester Hans Bouwmeester Hans Bouwmeester Sjef Boeren, Sjef Boeren, Hans Bouwmeester

Summary

When polystyrene nano- and microplastics pass through simulated gastrointestinal digestion, they acquire a coating of gut proteins — a 'protein corona' — that dramatically increases their uptake by human immune cells (macrophages), boosting internalization of small neutral particles by up to six-fold compared to undigested plastic. The identity of the proteins driving this effect, including clotting factors and apolipoproteins, suggests that realistic dietary exposure conditions substantially change how microplastics interact with the body, and that lab tests using undigested plastics likely underestimate actual cellular uptake.

Polymers

Body Systems

Digestive Immune

Study Type In vitro

Abstract Background: Micro- and nanoplastics (MNPs) represent one of the most widespread environmental pollutants of the 21 st century to which all humans are orally exposed. Upon ingestion, MNPs pass harsh biochemical conditions within the gastrointestinal tract, causing a unique protein corona on the MNP surface. Little is known about the digestion-associated protein corona and its impact on the cellular uptake of MNPs. Here, we systematically studied the influence of gastrointestinal digestion on the cellular uptake of neutral and charged polystyrene MNPs using THP-1-derived macrophages. Results : The protein corona composition was quantified using LC‒MS-MS-based proteomics, and the cellular uptake of MNPs was determined using flow cytometry and confocal microscopy. Gastrointestinal digestion resulted in a distinct protein corona on MNPs that was retained in serum-containing cell culture medium. Digestion increased the uptake of uncharged MNPs below 500 nm by 4.0- to 6.1-fold but did not affect the uptake of larger sized or charged MNPs. Forty proteins showed a good correlation between protein abundance and MNP uptake, including coagulation factors, apolipoproteins and vitronectin. Conclusion: This study provides quantitative data on the presence of gastrointestinal proteins on MNPs and relates this to cellular uptake, underpinning the need to include the protein corona in hazard assessment of MNPs.

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