Origin-of-life researchers have a lot of explaining to do. In the last 70 years, our appreciation for the required complexity of the simplest forms of life has grown exponentially, while prebiotically plausible explanations for life’s required components remain elusive. One possible exception involves the formation of cell membranes. The basic structure of all cell membranes is a phospholipid bilayer. Phospholipids (or more generally, amphiphilic molecules) naturally form into spherical bilayers when placed in water under the right conditions.1
Do cell membranes really form by purely natural processes? The latest video in the Long Story Short series, released yesterday on YouTube, addresses this claim.
Cell membranes are essential for life because they actively maintain homeostasis, providing a consistent environment inside the cell despite varying conditions outside. To accomplish this, they must be actively and selectively permeable — passing essential nutrients into the cell and pushing waste products out.
A simple membrane composed only of phospholipids is too tight — it does not allow adequate transportation across the membrane, thus converting the inner contents to a tomb for decaying components and accumulating waste. Some researchers have therefore suggested that early “proto-membranes” were leaky, composed of simpler amphiphilic molecules.2 But simple leaky membranes are no better at maintaining homeostasis than are simple tight membranes.
In life, membranes face conflicting requirements such as keeping very small items out while allowing substantially larger items in. For example, membranes pump protons out and must not allow the protons to pass freely back in, but they must also transfer larger nutrient molecules like histidine into the cell. The challenge is that histidine is about 700,000 times the size of a proton. Cells must also allow water to enter, but water facilitates a free flow of protons and cells cannot allow protons to flow freely. No degree of “leakiness” in a membrane will succeed in keeping protons out while allowing histidine and water in.
How can any membrane meet such dramatically conflicting requirements? All cellular life employs a variety of highly specialized protein channels and active transport systems in the membrane. Mycoplasma genitalium, one of the simplest forms of single-celled life, produces about 140 different proteins that serve these functions within the cell membrane.3 Of all the known proteins produced by living organisms, about a third operate within membranes.4 To maintain homeostasis, these protein channels must be highly specific, allowing only particular molecules to pass in a particular direction. A phospholipid bilayer that incorporates 140 different complex proteins bears almost no resemblance to the simple “membranes” that can be produced by prebiotic processes.
One of the Simplest Cells
Whereas complex cells can manufacture essential nutrients from simple feedstock molecules, simpler cells must import more of the necessary nutrients. Therefore, transportation of a variety of molecules across the membrane actually becomes more important in simpler cells. The majority of the required protein channels consume energy (in the form of ATP).5 A recent study proposed that membrane transport accounts for approximately 20 percent of energy consumption in one of the simplest known cells, JVCI Syn3A.6
Another layer of required complexity of cell membranes is the fundamental asymmetry of the bilayer: the inner (cytoplasmic) leaflet contains different lipids and protein orientations from the outer (extracellular) leaflet.7 For example, glycolipids are always found in the outer leaflet. No prebiotic natural process can produce this type of asymmetric lipid bilayer.
The very simple “membranes” produced by placing amphiphilic molecules in water are more like soap bubbles or lava lamps than actual cell membranes. Suggesting that cell membranes are easy to produce in prebiotic conditions demonstrates a fundamental ignorance of the function of cell membranes. To sustain life, membranes must have been complex from the very start — actively and selectively permeable. Yes, origin-of-life researchers have a lot of explaining to do, even when it comes to cell membranes.
- Lombard J, Lopez-Garcia P, Moreira D. The early evolution of lipid membranes and the three domains of life. Nature Reviews Microbiology 2012. 10; 507-515.
- Mansy SS et al. Template-directed synthesis of a genetic polymer in a model protocell. Nature. 2008; 454: 122-125.
- Fraser CM et al. The minimal gene complement of Mycoplasma genitalium. Science. 1995; 270; 397-403.
- Poetsch A, Wolters D. Bacterial membrane proteomics. Proteomics. 2008; 8: 4100-4122.
- Santos, JA et al. Functional and structural characterization of an ECF-type ABC transporter for vitamin B12. eLife. 2018; 7: e35828.
- Thornburg ZR et al. Fundamental behaviors emerge from simulations of a living minimal cell. Cell 2022; 185: 345-360.
- Dingjan T, Futerman AH. The fine-tuning of cell membrane lipid bilayers accentuates their compositional complexity. BioEssays 2021; 43: 2100021. DOI: 10.1002/bies.202100021.