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Journal article
Graphene microsheets enter cells through spontaneous membrane penetration at edge asperities and corner sites
Proceedings of the National Academy of Sciences - PNAS, v 110(30), pp 12295-12300
23 Jul 2013
PMCID: PMC3725082
PMID: 23840061
Abstract
Understanding and controlling the interaction of graphene-based materials with cell membranes is key to the development of graphene-enabled biomedical technologies and to the management of graphene health and safety issues. Very little is known about the fundamental behavior of cell membranes exposed to ultrathin 2D synthetic materials. Here we investigate the interactions of graphene and few-layer graphene (FLG) microsheets with three cell types and with model lipid bilayers by combining coarse-grained molecular dynamics (MD), all-atom MD, analytical modeling, confocal fluorescence imaging, and electron microscopic imaging. The imaging experiments show edge-first uptake and complete internalization for a range of FLG samples of 0.5- to 10-mu m lateral dimension. In contrast, the simulations show large energy barriers relative to k(B)T for membrane penetration by model graphene or FLG microsheets of similar size. More detailed simulations resolve this paradox by showing that entry is initiated at corners or asperities that are abundant along the irregular edges of fabricated graphene materials. Local piercing by these sharp protrusions initiates membrane propagation along the extended graphene edge and thus avoids the high energy barrier calculated in simple idealized MD simulations. We propose that this mechanism allows cellular uptake of even large multilayer sheets of micrometer-scale lateral dimension, which is consistent with our multimodal bioimaging results for primary human keratinocytes, human lung epithelial cells, and murine macrophages.
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Details
- Title
- Graphene microsheets enter cells through spontaneous membrane penetration at edge asperities and corner sites
- Creators
- Yinfeng Li - Brown UniversityHongyan Yuan - Brown UniversityAnnette von dem Bussche - Brown UniversityMegan Creighton - Brown UniversityRobert H. Hurt - Brown UniversityAgnes B. Kane - Brown UniversityHuajian Gao - Brown University
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 110(30), pp 12295-12300
- Publisher
- Natl Acad Sciences
- Number of pages
- 6
- Grant note
- P42 ES013660 / Superfund Research Program of the National Institute of Environmental Health Sciences 1028530 / Directorate For Engineering; National Science Foundation (NSF); NSF - Directorate for Engineering (ENG) CMMI-1028530; CBET-1132446 / National Science Foundation; National Science Foundation (NSF) 1132446 / Div Of Chem, Bioeng, Env, & Transp Sys; National Science Foundation (NSF); NSF - Directorate for Engineering (ENG) P42ES013660 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemical and Biological Engineering
- Web of Science ID
- WOS:000322112300043
- Scopus ID
- 2-s2.0-84880675612
- Other Identifier
- 991021230001204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Materials Science, Multidisciplinary