Tensile strength of cell membranes

[Sophrosyne]

TL;DR Summary

What is the stress resistance of cell membranes and how is it achieved?

The structure of the cell membrane is depicted as being formed from a bilayer of phospholipids with their hydrophilic portions pointing outwards and their hydrophilic portions facing each other.

But as I look at the histology of the epithelial layer of the epidermis or mucous membranes, I am struck by how surprisingly tough they are. You really have to fall down pretty hard to skin your hand. You can pull hard on a rope, even supporting your full weight with it, and the epidermis of your hands can hold. That’s a lot of stress on the material! It’s not at all like what happens with soap bubbles- what is often invoked as a model to explain the hydrophilic/hydrophobic interactions forming cell membranes.

Where is that strength coming from? I know there are desmosomes and hemi-desmosomes holding the cells together. But these proteins still are have anchored into the cell membrane. So the cell membrane itself still has to be pretty tough. Is this really achieved purely through hydrophilic/hydrophobic interactions between the phospholipids in the membranes? I find that hard to believe. There are no covalent bonds between these molecules either, as far as I know.

Thanks in advance.

 

[BillTre]

Consider the relationship between the membrane and the proteins (and perhaps other non-lipid molecules inserted into it) as a two way thing.
While the membrane will control where the lipophilic parts of proteins go to some degree, the arrangement of the lipophilic protons of proteins (or other molecules), in 3D space, can also determine where the membrane they are interacting with goes in 3D space and add their properties to the whole. As a layer of proteins inserted into a membrane move, so will the membrane lipids.

Interactions among neighboring proteins (like clathrin) in a membrane are involved in deforming the membrane to do things like pinch off vesicles.
A great mass of lipophilc molecules (and what ever they are in turn linked to), inserted into the membrane will determine the shape of that membrane in 3D space. The linkages to proteins (and other molecules) will, to a large extent, determine the deviations of the membrane from a sphere, which would be its lowest energy configuration.
Associated proteins (and other molecules), inside and outside the cell (as well as many layers of cells and dead cells (epidermis)), can provide the toughness you describe.

These things are all very small, but in large numbers, their little strengths can add up.

 

[Sophrosyne]

I see.

But let’s talk about the oral mucosa, since the skin has a thick keratin layer that can be a confounding variable. The stratified squamous epithelial cell layer in the oral cavity is only about 5 cell layers thick. Doubling that number for the number of cell membranes aligned parallel to any shearing forces will mean there are only 10 molecular phospholipid layers resisting any force parallel to it. That means a vigorous brushing with a relatively massive toothbrush should easily be able to break all these hydrophobic/hydrophilic bonds (especially since toothpaste is a surfactant also and should weaken those hydrophobic/hydrophilic interactions). I can’t imagine that hydrophobic/hydrophilic interactions alone, even with the proteins in them, can be THAT powerful.

 

[BillTre]

There is no doubt in my mind that a lipid bilayer without proteins would not be very mechanically strong.
Instead of your complex examples you might want to consider other examples with less possible structural support from proteins in the membrane.
For example, non-adherent eukaryotic cells with no cell wall in tissue culture. I have cultured loose myeloma cells (that look like shiney, clear marbles, in a phase microscope). They are more fragile like you are describing.
Cells in intact tissues are often "dissociated" to free them up to put single cells in tissue culture. Protein degrading enzymes are used as well as mechanical disruption. Many cells die, some pop out free of the others. They are probably also fragile.

Another example is sticking cells with microelectrodes. For many cells, there not that much resistance to the electrode going into the cell (going through the membrane).

It would be interesting to know what percentage of membrane surface area is composed of membrane proteins vs. the lipids in these more complex tissue situations your describing. There might be studies on this. I don't know. One possible way to look at it would be looking at freeze fracture images of the cell membrane in question. There are probably other ways also.
Both intracellular and extracellular proteins, joined to membrane proteins, would provide additional mechanical strength to cells in tissues.

In either case, I would expect big differences in what you are seem to be calling something like membrane strength with and without proteins (and their extracellular and intracellular supporting proteins) in the membranes.

 

[Sophrosyne]

There is no doubt in my mind that a lipid bilayer without proteins would not be very mechanically strong.
Instead of your complex examples you might want to consider other examples with less possible structural support from proteins in the membrane.
For example, non-adherent eukaryotic cells with no cell wall in tissue culture. I have cultured loose myeloma cells (that look like shiney, clear marbles, in a phase microscope). They are more fragile like you are describing.
Cells in intact tissues are often "dissociated" to free them up to put single cells in tissue culture. Protein degrading enzymes are used as well as mechanical disruption. Many cells die, some pop out free of the others. They are probably also fragile.

Another example is sticking cells with microelectrodes. For many cells, there not that much resistance to the electrode going into the cell (going through the membrane).

It would be interesting to know what percentage of membrane surface area is composed of membrane proteins vs. the lipids in these more complex tissue situations your describing. There might be studies on this. I don't know. One possible way to look at it would be looking at freeze fracture images of the cell membrane in question. There are probably other ways also.
Both intracellular and extracellular proteins, joined to membrane proteins, would provide additional mechanical strength to cells in tissues.

In either case, I would expect big differences in what you are seem to be calling something like membrane strength with and without proteins (and their extracellular and intracellular supporting proteins) in the membranes.

Whatever it is, it’s still hard to imagine ANY hydrophobic/hydrophilic interactions having THAT much strength, no matter how many of them there are or how many proteins are thrown in there. A chain is only as strong as its weakest link. If that’s really where that strength comes from, it’s truly impressive. I would have thought that only strong covalent bonds, such as with cross-linked collagen fibers, would be able to have so much strength. Impressive!

I wonder if some smart physical chemist or material scientist can actually calculate the strength of such non-covalent interactions in the membrane.

 

[Ygggdrasil]

Biophysicists have done some research recently on this issue and found that membrane proteins within the lipid bilayer and their attachment to the underlying cytoskeleton inside the cell play important roles:

Cell Membranes Resist Flow
Shi et al. Cell 175:1769 (2018)
https://www.sciencedirect.com/science/article/pii/S0092867418313059?via=ihub

Summary

The fluid-mosaic model posits a liquid-like plasma membrane, which can flow in response to tension gradients. It is widely assumed that membrane flow transmits local changes in membrane tension across the cell in milliseconds, mediating long-range signaling. Here, we show that propagation of membrane tension occurs quickly in cell-attached blebs but is largely suppressed in intact cells. The failure of tension to propagate in cells is explained by a fluid dynamical model that incorporates the flow resistance from cytoskeleton-bound transmembrane proteins. Perturbations to tension propagate diffusively, with a diffusion coefficient Dσ ∼0.024 μm2/s in HeLa cells. In primary endothelial cells, local increases in membrane tension lead only to local activation of mechanosensitive ion channels and to local vesicle fusion. Thus, membrane tension is not a mediator of long-range intracellular signaling, but local variations in tension mediate distinct processes in sub-cellular domains.

Do Cell Membranes Flow Like Honey or Jiggle Like Jello?
Cohen & Shi. BioEssays 42:1900142 (2019)
https://onlinelibrary.wiley.com/doi/full/10.1002/bies.201900142

Abstract

Cell membranes experience frequent stretching and poking: from cytoskeletal elements, from osmotic imbalances, from fusion and budding of vesicles, and from forces from the outside. Are the ensuing changes in membrane tension localized near the site of perturbation, or do these changes propagate rapidly through the membrane to distant parts of the cell, perhaps as a mechanical mechanism of long‐range signaling? Literature statements on the timescale for membrane tension to equilibrate across a cell vary by a factor of ≈106. This study reviews and discusses how apparently contradictory findings on tension propagation in cells can be evaluated in the context of 2D hydrodynamics and poroelasticity. Localization of tension in the cell membrane is likely critical in governing how membrane forces gate ion channels, set the subcellular distribution of vesicle fusion, and regulate the dynamics of cytoskeletal growth. Furthermore, in this study, it is proposed that cells can actively regulate the degree to which membrane tension propagates by modulating the density and arrangement of immobile transmembrane proteins. Also see the video abstract here .

 

[Sophrosyne]

Biophysicists have done some research recently on this issue and found that membrane proteins within the lipid bilayer and their attachment to the underlying cytoskeleton inside the cell play important roles:

Cell Membranes Resist Flow
Shi et al. Cell 175:1769 (2018)
https://www.sciencedirect.com/science/article/pii/S0092867418313059?via=ihub

SummaryDo Cell Membranes Flow Like Honey or Jiggle Like Jello?
Cohen & Shi. BioEssays 42:1900142 (2019)
https://onlinelibrary.wiley.com/doi/full/10.1002/bies.201900142

Abstract

This is interesting stuff. Thank you!

 

[Sophrosyne]

There is no doubt in my mind that a lipid bilayer without proteins would not be very mechanically strong.
Instead of your complex examples you might want to consider other examples with less possible structural support from proteins in the membrane.
For example, non-adherent eukaryotic cells with no cell wall in tissue culture. I have cultured loose myeloma cells (that look like shiney, clear marbles, in a phase microscope). They are more fragile like you are describing.
Cells in intact tissues are often "dissociated" to free them up to put single cells in tissue culture. Protein degrading enzymes are used as well as mechanical disruption. Many cells die, some pop out free of the others. They are probably also fragile.

Another example is sticking cells with microelectrodes. For many cells, there not that much resistance to the electrode going into the cell (going through the membrane).

It would be interesting to know what percentage of membrane surface area is composed of membrane proteins vs. the lipids in these more complex tissue situations your describing. There might be studies on this. I don't know. One possible way to look at it would be looking at freeze fracture images of the cell membrane in question. There are probably other ways also.
Both intracellular and extracellular proteins, joined to membrane proteins, would provide additional mechanical strength to cells in tissues.

In either case, I would expect big differences in what you are seem to be calling something like membrane strength with and without proteins (and their extracellular and intracellular supporting proteins) in the membranes.

So the picture that’s emerging for me is a complex scaffolding of intra- and intracellular proteins which provide the true structural strength of the epithelium with their strong covalent bonds, and the phospholipid layer does not contribute much to this structural integrity. That makes more sense.

 

[BillTre]

So the picture that’s emerging for me is a complex scaffolding of intra- and intracellular proteins which provide the true structural strength of the epithelium with their strong covalent bonds, and the phospholipid layer does not contribute much to this structural integrity. That makes more sense.

Yes!
The lipid bilayers main importance is separating two ionic (aqueous) domains, the inside and outside of cells (or internal bits of cells). This distinction underlies many life functions.

 

[Sophrosyne]

Thank you for these informative replies. This has been very helpful.

A slightly tangential question I have also had is why surfactants like toothpaste or soap do not disrupt these surface membranes like the oral mucosa quickly. Even eating greasy foods, I would think, could disrupt these membranes. It seems like they should easily be able to disrupt the hydrophilic/hydrophobic milieu and take off the epithelium like dissolving away grease.

I had heard set Lasik surgeons, for example, in wanting to do laser surgery on the corneal stroma, use a short application of alcohol to take off the corneal epithelium prior to the laser treatment. If it works with alcohol, why wouldn’t it work with getting soap in your eyes- or eating greasy food taking off your oral mucosa?

 

[pinball1970]

Thank you for these informative replies. This has been very helpful.

A slightly tangential question I have also had is why surfactants like toothpaste or soap do not disrupt these surface membranes like the oral mucosa quickly. Even eating greasy foods, I would think, could disrupt these membranes. It seems like they should easily be able to disrupt the hydrophilic/hydrophobic milieu and take off the epithelium like dissolving away grease.

I had heard set Lasik surgeons, for example, in wanting to do laser surgery on the corneal stroma, use a short application of alcohol to take off the corneal epithelium prior to the laser treatment. If it works with alcohol, why wouldn’t it work with getting soap in your eyes- or eating greasy food taking off your oral mucosa?

Reminds me of another thread.

https://www.physicsforums.com/threads/why-doesnt-soap-or-oil-destroy-your-skins-epidermis.973536/

 

[Sophrosyne]

Reminds me of another thread.

https://www.physicsforums.com/threads/why-doesnt-soap-or-oil-destroy-your-skins-epidermis.973536/

Yeah, no one really seemed to have a good solid answer on that one. I was hoping that by giving it another whirl here it might turn something up.

It’s funny, I have asked this of some MDs and PhDs and really have not gotten a good response either. They just give me a puzzled look, and it’s clear it’s not something they have really thought about much. It might be a good project for someone!

This is as close as I have come:
https://pubmed.ncbi.nlm.nih.gov/24827732/

But I am not sure why the detergents/surfactants used there in endothelial cells don’t apply to epithelial cells everywhere. Is it just a matter of concentration?