Physical properties of the bacterial outer membrane
Open accessAbstract
It has long been appreciated that the Gram-negative outer membrane acts as a permeability barrier, but recent studies have uncovered a more expansive and versatile role for the outer membrane in cellular physiology and viability. Owing to recent developments in microfluidics and microscopy, the structural, rheological and mechanical properties of the outer membrane are becoming apparent across multiple scales. In this Review, we discuss experimental and computational studies that have revealed key molecular factors and interactions that give rise to the spatial organization, limited diffusivity and stress-bearing capacity of the outer membrane. These physical properties suggest broad connections between cellular structure and physiology, and we explore future prospects for further elucidation of the implications of outer membrane construction for cellular fitness and survival.
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The discrepancy in sensitivity between Gram-positive and Gram-negative bacteria is primarily due to fundamental structural and compositional differences in their cell envelopes.
“This discrepancy is primarily due to fundamental structural and compositional differences in their cell envelopes.”
From Influence of Extraction Parameters on Bioactive Compounds and Antimicrobial Activity of Banana Peel Using Ethanol-Water Solvent (2026) · cites this paper as Sun et al., 2022
The Introduction (page unavailable) describes structural and compositional differences between Gram-positive and Gram-negative cell envelopes and says the Gram-negative outer membrane provides resistance to large, hydrophobic antibiotics that are effective against Gram-positive bacteria. This supports an envelope-based explanation for that specific sensitivity difference, but the source does not establish that envelope differences are the primary cause of sensitivity differences in general. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe outer membrane of Gram-negative bacteria limits the penetration of antimicrobial substances, including polyphenols and other phytochemicals, thereby reducing their effectiveness against Gram-negative species.
“This outer membrane effectively limits the penetration of a wide range of antimicrobial substances, including polyphenols and other naturally occurring phytochemicals, thereby reducing the effectiveness of these agents against Gram-negative species (Sun et al., 2022; Ghosh et al., 2025).”
From Influence of Extraction Parameters on Bioactive Compounds and Antimicrobial Activity of Banana Peel Using Ethanol-Water Solvent (2026) · cites this paper as Sun et al., 2022
The Introduction describes the Gram-negative outer membrane as a permeability barrier that confers resistance to large and hydrophobic antibiotics, and says it hinders passage of hydrophobic molecules. It does not specifically address polyphenols or other phytochemicals, or establish that this barrier reduces their effectiveness against Gram-negative species. No page numbers are provided in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredGram-negative bacteria have an additional outer membrane rich in lipopolysaccharides that functions as a formidable permeability barrier.
“Gram-negative bacteria are characterized by the presence of an additional outer membrane that is rich in lipopolysaccharides, which functions as a formidable permeability barrier.”
From Influence of Extraction Parameters on Bioactive Compounds and Antimicrobial Activity of Banana Peel Using Ethanol-Water Solvent (2026) · cites this paper as Sun et al., 2022
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Cites
Molecular Basis of Bacterial Outer Membrane Permeability Revisited
Nikaido, H. (2003) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.67.4.593-656.2003 · Cited by 4,316 · see citing works
Murein segregation in Escherichia coli
de Pedro, M. A., Quintela, J. C., Höltje, J. V., & Schwarz, H. (1997) · Journal of Bacteriology · doi:10.1128/jb.179.9.2823-2834.1997 · Cited by 388 · see citing works
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Cited by
Sorted by citations
İmece, A. (2026) · Journal of the Institute of Science and Technology · doi:10.21597/jist.1745262
- Authors
- Sun, J., Rutherford, S. T., Silhavy, T. J., & Huang, K. C.
- Affiliations
- Stanford University (US)
- Genentech (US)
- Princeton University (US)
- Chan Zuckerberg Biohub San Francisco (US)
- Corresponding author
- Rutherford, Steven T.
- Silhavy, Thomas J.
- Huang, Kerwyn Casey
- Venue
- Nature Reviews Microbiology
- Published
- 2021-11-03
- Volume
- 20
- Issue
- 4
- Pages
- 236-248
- ISSN
- 1740-1526 (ISSN-L)
- 1740-1534
- PMC
- PMC8934262
- OpenAlex
- W3208774826
- Cited by
- 404
- References
- 3
- Citations by year
- 2026: 88 · 2025: 125 · 2024: 107 · 2023: 62 · 2022: 22
- FWCI
- 7.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Reviews Microbiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r35gm118024-10)
- National Institute of General Medical Sciences (R35-GM118024, RM1GM135102)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
- Keywords
- bacterial outer membrane, Gram-negative bacteria, membrane permeability barrier, membrane mechanics, membrane rheology, membrane diffusivity
- MeSH terms
- Bacterial Outer Membrane, Bacterial Outer Membrane Proteins, Cell Membrane, Gram-Negative Bacteria, Permeability
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