3/12/97




Hi!

Can someone explain the relation between the tonicity and osmolarity

of a fixation solution?

Gary Dietrich Chinga

garyc@stud.ntnu.no


Osmolarity is an easily measurable characteristic, by e.g. freezing point

depression. In simple terms it is the total concentration of solutes

(including ions) in a solution, and this does not depend on whether the

solutes can cross cell membranes or not. Tonicity relates to the osmotic

GRADIENT due to solutes that affects a semi-permeable membrane ( i.e.

a membrane that is permeable to water); ONLY solutes that do not cross

the membrane contribute to this effect. The two characteristics are

different and obviously have vastly different consequences on

membranes. Weak bases, even though ionized, have some measurable

permeability and so their contribution to tonicity must be much less than

their contribution to osmolarity. Osmium is hydrophobic and quite

permeable through membranes, so contributes *nothing* to an osmotic

gradient that can disrupt the membranes (even assuming it doesn't alter

their permeability to tonic agents like sucrose). So osmium contributes

nothing to tonicity, but certainly does contribute to osmolarity.

I personally wonder how to express the tonicity of compounds that are

somewhat permeable, such as weak bases or short carboxilic acids &

aldehydes. I guess the concept of tonicity either doesn't apply or is

operational in such cases, depending on the time scale of interest. Can

anyone comment or give a reference to a good detailed textbook?

Something about reflection coefficients?

Richard Thrift

Richard_Thrift@depotech.com


Gary,

Tonicity is a relative, unitless comparison of one solution to

another in which the first solution (presumably the water in your tissue

sample) is hypertonic, hypotonic or isotonic to the second solution

(presumably your fixative). Osmolarity is an absolute scale (usually in

some type of pressure unit) which describes the concentration of osmolytes

in a single solution. So you need to know the osmolarity of your tissue so

you can set the osmolarity of your fixative to be isotonic with respect to

the tissue.

Robert R. Wise

Plant Physiologist and Director, UWO Electron Microscope Facility

Department of Biology

University of Wisconsin Oshkosh

Oshkosh, WI 54901

(414) 424-3404 tel

(414) 424-1101 fax

wise@uwosh.edu


Osmolarity is a measure of one of the colligative properties (osmotic

pressure) of a solution. In a rough sense it is the measure of the amount

of solute in a solution, but the degree of dissociation of the solute

affects its osmolarity, so osmolarity is not necessarily a direct measure

of molar concentration. (For example, a 1 molar solution of NaCl will

have *approximately* twice the osmotic pressure [osmolarity] of a 1 molar

solution of sucrose, since the NaCl dissociates into 1 molar Na+ and

1 molar Cl-.)

Two solutions (not necessarily of the same solute or of a single solute)

are isosmotic if they have the same osmolarity (osmotic pressure). If two

isosmotic solutions are placed on opposite sides of a semipermeable

membrane, the osmotic pressure on each side is the same and there is no

*net* movement of water across the membrane. However, if the osmolarity

of the two solutions is not the same, then water will move across the

membrane from the hypo-osmotic solution (more dilute) to the hyperosmotic

solution (less dilute) until the osmotic pressure on each side is equal

(a number of other factors affect this as well, but let's ignore them

here).

Tonicity refers to the response of *cells or tissues* to the solutions in

which they are immersed. If cells are placed in a hypertonic solution,

net movement of water will be out of the cell, causing the cell to

shrivel. If cells are placed in a hypotonic solution, net movement of

water will be into the cell, causing the cell to swell or burst. Tonicity

is useful only in reference to a particular cell or tissue.

Thus, the microscopist wishes to add sufficient solute(s) to the fixation

solution so that the solution has the correct osmolarity (measured in

milliosmols) so that it will have the desired tonicity with respect to the

cells that are being exposed to the fixative. [There is debate whether

the solution should be slightly hypertonic or hypotonic, but then that is

another subject about which we may choose to debate.]

To summarize, osmolarity is a measurement of solute concentration

(measurement can be made in a beaker). Tonicity is a comparison of

osmolarities between a cell and the solution to which it is exposed.

I hope that this does not leave readers more confused than they were

before.

Donald L. Lovett e-mail: lovett@tcnj.edu

Assoc. Professor, Dept. of Biology voice: (609) 771-2876

The College of New Jersey fax: (609) 771-2674

Trenton, NJ 08650-4700


Donald Lovett's explanation quoted below is very good except that it

perpetuates the myth that tonicity is related to the difference between

two OSMOLARITIES on opposite sides of the membrane. That is ONLY

true if the membrane involved is impermeable to ALL of the solutes

contributing to the osmolarity. Since formaldehyde is soluble in both

benzene and chloroform I expect it to be quite permeable across cell

membranes. Thus it will contribute to osmolarity, but should contribute

little to tonicity. The tonicity of your fixative should be adjusted with other

components, and the final osmolarity of an isotonic fixative will be approx

300 mOsm PLUS the value of osmolarity contributed by the formaldehyde

present.

To reiterate, IF a compound is permeable across the membrane it

contributes to osmolarity but does not contribute to the osmotic

GRADIENT. Thus it does NOT contribute to tonicity.

Caveats: Practically speaking, the rate at which a permeable solute

crosses the membrane will affect the transient forces on the membrane.

I assume tonicity is ill-defined unless the system is at equilibrium. The

situation becomes even more complicated if the compounds added (such

as aldehydes or alcohols) alter the permeability of the membrane for

other buffer components present. And if differences in rates of

diffusion through a chunk of tissue are involved, are we really still talking

about tonicity?? That calls for empirical, not theoretical, optimization of

the recipe used !!

On that note, how many of you microscopists have actually compared

e.g. confocal images of cell cultures fixed with buffers of different

tonicity with equivalent images of live cultured cells? The time to diffuse

through a monolayer of cells should be negligible. What do you find is

optimum?

Richard Thrift

Richard_Thrift@depotech.com


Thanks for your extended clarification of the subject. I agree entirely

with your comments. I had tried to focus on the difference between

the two terms and simplify my response with the caveat:

>

> "(a number of other factors affect this as well, but let's ignore them

here)."

>

I also agree that the response of the cell to the solution (as evaluated

by trial and error) is the most important aspect to microscopists,

irrespective of how one names or measures the composition of the solution.

Donald L. Lovett e-mail: lovett@tcnj.edu

Assoc. Professor, Dept. of Biology voice: (609) 771-2876

The College of New Jersey fax: (609) 771-2674

Trenton, NJ 08650-4700


i

In reguards to the question of tonicity, does anyone know the best

percentage of sucrose to have in a primary Zamboni fixative(2% para and

15% picric acid in sorensons) to fix cell cultures in order to minimize

any cell distortion.

Thanks in advance

Bob Underwood

Morphology core

University of Washington

underwoo@u.washington.edu


I can't give a specific answer, but check out Maser MD et al: Relationships

among pH, osmolality and concentration of fixative solutions, Stain

Technology 42:175-182 (1967). You need to know what osmolality you want in

the fixative solution. Around 300 milliosmols (range 200-400) seemed to be

most common when I had to work it out too many years ago. In general the

contribution of the fixative can be ignored. So, work out the osmolality of

the buffer and add sucrose to bring the osmolality up to the total. For

instance, Sorensen's is approx 105 at 0.05M, approx 210 at 0.1M. Sucrose is

obvious (eg 0.2M = 200). It may be an idea to add some CaCl2 or MgCl2.

Diana van Driel

Dept Ophthalmology

Sydney University C09

AUSTRALIA 2006

dianavd@eye.usyd.edu.au


In the theme of Diana van Driel's post check out Arborgh et al. "The

osmotic effect of glutaraldehyde during fixation". J. Ultrastr. Res.

56:339-350, 1976. A very interesting and through study.

Geoff McAuliffe, Ph.D.

Neuroscience and Cell Biology

Robert Wood Johnson Medical School

675 Hoes Lane Piscataway, NJ 08854

voice: (908)-235-4583; fax -4029 e-mail: mcauliff@umdnj.edu


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