The Microtrabecular Lattice MTL

New techniques in electron microscopy developed by Keith Porter and colleagues (1981) at the University of Colorado at Boulder have led to observation of an irregular three dimensional lattice of slender strands throughout the cytoplasm, interconnecting nearly everything in the cell. The interlinked filaments appear to suspend the various cell systems, organelles, and larger cytoskeletal elements such as microtubules and filaments with a matrix material continuous with the individual lattice filaments. The lattice is suggestive of the trabecular structure of spongy bone and it was named the microtrabecular lattice (MTL, Figure 5.19).

Porter and colleagues took advantage of the properties of the high voltage electron microscope at Boulder. This massive device is capable of accelerating electrons across a potential drop of a million volts, ten times that of standard electron microscopes. The extra voltage gives the electrons sufficient energy to penetrate thick specimens or even intact cells up to several thousand nanometers thick. Previously, cells had to be sliced into sections thinner than 200 nanometers, and artifacts due to cell destruction were more prevalent. The high voltage electron microscope provides more information about depth, giving a three dimensional view of cell organization. Another innovation, the critical point drying method (Ellisman, 1981) avoids the distorting effect of surface tension which causes cells to collapse when they are dried in air. High voltage electron microscopy and critical point drying have now demonstrated the MTL in all eukaryotic cells which have been examined.

The MTL is a three dimensional lattice of slender strands called microtrabeculi. They range in diameter from 4 to 10 nanometers with lengths of 10 to 100 nanometers. The MTL is a finely organized meshwork that divides the ground substance into two phases, a protein rich polymerized phase comprising the MTL, and a water rich fluid phase that fills the intratrabecular spaces. At high magnification, microtrabeculi of the ground substance are seen to crosslink many elements in the cytoplasm. For example, they connect microtubules with the smooth endoplasmic reticulum. The MTL not only crosslinks, but appears to be dynamically active in moving elements through the cytoplasm. The dynamic MTL moves material in a saltatory manner at velocities equivalent to axoplasmic transport. A co-pioneer with Porter in the observation of cytoplasmic ground structure, Mark Ellisman (1981) of the University of California at San Diego has observed that MT and filaments are analogous to rigid skeletal elements such as bone, and that the microtrabecular lattice may be appropriately equated with work producing components such as skeletal musculature. Thus Ellisman suggests a more appropriate description of the MTL might be "cytomusculature."

In neurons, wispy MTL strands radiate from MT and neurofilaments at right angles into the cytoplasm, often interconnecting MT with other MT and neurofilaments with neurofilaments. At the synapse, the MTL appears intimately involved in both neurotransmitter release and post synaptic receptor mechanisms. Presynaptic terminals demonstrate notable MTL crosslinking among synaptic vesicles and among vesicles and synaptic membranes. In post synaptic dendrite MTL, linkages are visible among filamentous subsynaptic densities and the other elements of dendritic cytoplasm. Where axonal cytoplasm enters synaptic regions, transitions occur in the form of the MTL. In axons, cross linkages are clearly exhibited between MT, filaments, and other components. However, in presynaptic terminals and dendrites, the MTL network is more similar in structure to isolated actin-myosin gels observed in non neuronal cells. Raymond Lasek (1981) of Case-Western Reserve University has shown that the cytoplasm of nerve axon growth cones, which differs from axonal cytoplasm, is rapidly converted from the axonal variety to the growth cone variety in axons severed from their cell bodies. Thus "local" factors appear able to transform axoplasm to synaptic terminal cytoplasm, or axoplasm to growth cone cytoplasm. The MTL is the fine structure and texture of cytoplasm.

MTL activities appear to be dependent on calcium ion concentration. Ellisman's work shows that high calcium exposure causes the MTL to shorten and deform, leaving free ends or "nubbins." In normal axoplasm, different forms of MTL corresponding to both high and low calcium ion concentration appear to be found concurrently. These may correspond with "sol" and "gel" states determined by other techniques. Ellisman suggests that calcium may be the coupling agent for the dynamic aspects of the MTL in terms of location, extent and form of crossbridging of cellular constituents. Calcium regulated by cytoskeletal structures, or membranes, and the MTL itself may be locally dynamic and patterned. Standing waves, dissipative patterns, or holograms "hardwired" in MTL could be representations of calcium coupled states in cytoplasm.

Figure 5.19: Microtrabecular lattice (MTL) in PtK2 cell cytoplasm. Microtubules can be seen (one rising left to right on bottom) in the background of microtrabecular lattice (MTL). Two 40 nanometer gold particles are trapped in a vesicle within the MTL. With permission from DeBrabander (1985).

Ellisman raises the question of the importance of the cytoskeleton and MTL in the nervous system. One consideration is modulation of membrane related events such as receptor activity and neurotransmitter extrusion. Ellisman proposes that the MTL is triggered by calcium ions to release neurotransmitter vesicles. In addition, the MTL participates in other cytoskeletal functions also involving MT and filaments. These are axoplasmic transport, turnover and maintenance of membrane proteins and receptors, and the availability of neurotransmitters and enzymes at synapses. Ellisman has predicted some of the functions and/or behavior of the cytoskeleton and MTL within the nervous system. These are: 1) the MTL is a substrate to maintain cell shape changes including synaptic formation, and to regulate excitable properties of neurons. One example would be changes in distribution and volume of dendritic spines and synapses with implications for synaptic connections and perhaps learning and memory. Thus the MTL and other cytoskeletal elements can modify synaptic function by participating in trophic maintenance and turnover of membrane proteins to modulate membrane excitability and neuronal signaling. 2) The MTL, according to Ellisman, can also buffer small molecules and ions, maintaining these in specialized locations and patterns for metabolic and electrical functions. Thus the MTL may compartmentalize the cell, forming regions whose environments may vary. Buffering and control of calcium ion flux may be particularly important, and directly relate to cognitive functions. 3) The MTL can differentiate specific zones of cytoplasm and membrane, for example controlling the types of receptors or channels at synaptic zones by specific cytoskeletal linkages. The MTL and cytoskeleton also control the distribution of organelles, for example keeping the endoplasmic reticulum from entering axons, restricting the Golgi apparatus to perinuclear zones and keeping the synaptic bouton the right composition of axoplasm. 4) The MTL can mediate embryological development or morphogenesis through linkages with specific hormone receptors or tissue factors resulting in variations in developmental patterns. 5) The MTL can transduce chemical or mechanical work for intracellular transport and processes such as axoplasmic transport and translocation of synaptic vesicles to release sites on the presynaptic membrane. To Ellisman, the MTL regulates the rest of the cytoskeleton and the cell at large. In his view, it is the dynamic ground substance capable of intelligent behavior. One could argue, however, that MT regulate the MTL. What is most significant is the question of how they communicate.

The most labile and transient of the cytoskeletal levels of organization, the MTL is the current microfrontier of living material organization. The MTL is a network within a network of cytoskeletal proteins which, in the case of the nervous system, is a network within a network of neurons. In Chapter 8, a model of information processing will be discussed in which the MTL represents standing wave patterns of calcium coupled sol-gel states resulting from dynamic excitations of the cytoskeleton. Coherent excitations in the cytoskeleton could result in "holographic" standing waves which may be the bottom level of an information hierarchy: "infoplasm." An analog picture in which the MTL is both paint and canvas could be the texture of consciousness.

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