PURE ZETA: PART FOUR: IONS!
URE ZETA: PART FOUR: IONS!
Zeta potential is the surface charge on LNP (and other things!). Zeta potential not only determines WHERE it goes in the body, but WHAT it does (interactions).
It does not exist in a vacuum. It can change, based on many factors.
Today: IONS!
2/ IONS exist in the human body. They are not just in the form of metals. We have metals floating around in our body. Sodium (Na+) is a metal. It has a positive charge of +1. Potassium (K). Sodium chloride, what you eat, has two ions bound together, Cl- and Na+!
(IONIC BOND!)
3/ The bonds in salt (Cl- AND Na+) are called ionic because they both have an electrical charge— chloride (Cl-) ion is negatively charged and sodium ion (Na+) is positively charged.
These things can have what is called, a "strength". This is called IONIC STRENGTH. AND it varies!
4/ Ionic strength measures the amount of ions (charged particles) in solution, in terms of molarity (moles of ions per liter of solution). Solutions with higher ionic strength contain more ions, while solutions with lower ionic strength contain fewer ions. Ionic strength is an
5/important factor in the calculation of zeta potential, as it influences electrical properties (WHERE IT GOES AND WHAT IT INTERACTS WITH) of the solution (YOUR BODY, YOUR TISSUE, YOUR BLOOD) and the STABILITY of charged particles (IN THE CASE, THE LNP).
In a previous thread, I
6/ explained Debye length, which is critical in zeta potential calculation. It is the "cloud" we talked about. It defines how far the electrical influence of a charged particle extends into surrounding solution, and the electrostatic interactions it can have with other things.
7/ Debye length (λ_D) can be calculated:
λ_D = (ε * k * T) / (2 * N * e^2 * I)^0.5
λ_D is the Debye length.
ε : permittivity of solvent
k : Boltzmann's constant.
T : absolute temperature.
N : Avogadro's number.
e : elementary charge.
I : ionic strength of the solution
Is it
8/ obvious that ZETA and the charged surface on the LNP has a lot of factors going into it, which determines WHERE IT IS GOING TO GO IN THE BODY AND WHAT IT IS GOING TO DO?
The Debye length is inversely proportional to the square root of the ionic strength (I). As the ionic
9/ strength increases,Debye length decreases, and as Ionic strength decreases, Debye length increases.
in solutions of higher ionic strength (MORE IONS), Debye length is shorter, and electrostatic interactions between charged particles are more localized.
More localized: this
10/ means how charged particles "act" on one another is limited to a shorter distance within the solution. WHAT this means for LNP and zeta: If you have an LNP in HIGHER ions solution (like blood) the Debye length in solution is relatively short. This means electrostatic
11/ interactions between LNPs with a charge on them (- or +) and other charged particles, such as ions or proteins, act only over a short range. Just those within their close vicinity. BUT! (see how this is actually WORSE in some ways?) IF, that debye length is LONGER, INSIDE
12/ BLOOD VESSLES OR VEINS (OR HEART? HELLO!), the electrical influence of charged LNPs can extend over a greater distance within the solution (BLOOD/ TISSSUE!). Change in Debye length can have concerning implications for the behavior and interactions of charged particles (LNP).
13/ However, this could be good or bad, depending. If there is a higher debye length, with that charge, and say, it is negative, then it has a higher chance of repelling other negatively charged things (some proteins are) or ATTRACTING the things that have opposite charges (PF4)!
14/ Platelet factor 4 (PF4) is a 70-amino acid protein that is stored in alpha granules of platelets and is released on platelet activation [1]. PF4 is cationic, or positively charged, and forms tetramers at physiological pH and ionic strength (this will be explained later).
15/ 🚨🚨 "VITT occurs when antibodies attack a blood protein called platelet factor 4 (PF4). This activates platelets in the blood, causing them to clump together and form clots, the study authors explained." "Mechanisms of vaccine-induced thrombosis
https://www.nejm.org/doi/full/10.1056/nejmoa2105385
16/ 🚨🚨 Many blood proteins, such as albumin, globulins, and some enzymes, carry a POSITIVE charge. The charge on proteins is determined by the balance of positively and negatively charged amino acid residues within their structure (NEXT THREAD!!)
Hemoglobin: POSITIVE CHARGE.
17/ 🚨🚨 Various particles and metabolites in blood, such as amino acids, peptides, and some hormones, have a net positive charge! Would be terrible If an LNP gained a higher negative charge due to NEGATIVELY CHARGED DNA PLASMID CONTAMINATION.
Smaller particles have a larger
18/ surface area relative to their volume compared to larger particles. The surface charge is distributed over entire surface of LNP. As the size of LNP decreases, the surface charge density increases. So, what might be worse, SMALL LNP or BIG? "Bolus theory" shot down again!
19/!!! Smaller LNP experience STRONGER electrostatic interactions w/ ions IN THE BODY due to higher surface charge density. This results in significant repulsive or attractive forces between particles, depending on their surface charge and charge of surrounding ions. The
20/ "bolus" theory some scientists are supporting, is false.
LNP of different sizes may have different propensities to aggregate (CLUMP) or interact w/ particles i the body. Aggregation can alter the effective zeta potential of the particle clusters and CHANGE ZETA!
21/ The LNPs vary in size, before any aggregation, or absorption one lipids occur (Ostwald effect), flocculation, or ion bridging (see other thread). The bolus theory of that spider web mechanism is incorrect, and needs to go in the bin where it belongs.
22/ The zeta potential can differ when measured for particles of varying sizes within the range of 50 nm to 200 nm due to size-dependent factors and interactions with the surrounding medium (blood, tissues, solution, brain, organs, etc. )
The smaller LNP (50 nm) exhibits a
23/ stronger surface charge effect due to its higher surface area-to-volume ratio. This means, the smaller LNP, the individual LNP, having a non-neutral charge, of either positive or negative, will bind to things MORE, aggregate MORE, cause more harm (if it is doing harm), and
24/ do more overall damage compared to the larger ones (unless aggregation--blockages--aneurysm, LNP aggregates and binds with other things).
NEXT up--what happens when the LNP BINDS with other things, and how those can now interact with CELL RECEPTORS.