NPTEL – Biotechnology – Tissue Engineering

Direct cell-cell contact

S. Swaminathan
Director
Centre for Nanotechnology & Advanced Biomaterials
School of Chemical & Biotechnology
SASTRA University
Thanjavur 613 401
Tamil Nadu

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NPTEL – Biotechnology – Tissue Engineering

Table of Contents

1. DIRECT CELL-CELL CONTACT ........................................................................... 3

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NPTEL – Biotechnology – Tissue Engineering

1. Direct cell-cell contact

Cells exhibit special proteins on their surface leading to direct cell-cell contact. This
type of interaction is highly specific and direct communication between the two cells.
However, both soluble signalling and ECM signalling are non-specific since there is
no direct knowledge between the signalling cell and target cell. The cell-cell
signalling molecules are in two different forms. In the first form, the signal allows
mechanical contact between the two cells, whereas in the second, the molecule that
form junctions between the cells through which the molecules can be transported
from one cell to the other.

Let us see the cell junctions in animal epithelial tissue. There are four different
junctions facilitating the direct cell-cell interaction.
1. Tight junction: This can form the impenetrable barrier by sealing the
neighbouring cell membrane together. Thereby, it can prevent the
leakage of molecules between the cells.
2. Belt desmosomes: this is also called as adheren junctions. This can join
the actin cytoskeleton bundle of one cell to the similar bundle of the
adjacent cell. This can form a circumferential belt of adhesion.
3. Spot desmosomes: Also called as spot welds. This attaches the tough
intermediate filaments in one cell to the same in the neighbouring cell.
4. Gap junction: This can form a hollow channel between the adjacent cells
thereby allow the passage of small cytoplasmic molecules across the
membrane.

Tight junctions are the sheets of cells that can provide the interface between the cell
mass and a cavity or a space (lumen). A cell exposed to the lumen is the apical
surface and rest of the cell is called as a basolateral surface. This junction seals the
neighbouring epithelial cells in a narrow band just beneath their apical surface. This
will prevent the entry of molecules and ions across the space between the cells.
Materials can enter the cell only through diffusion or active transport. This junction
also blocks the movement of integral membrane proteins.
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Fig 1: Schematic of a tight junction

Adheren junctions provide strong mechanical attachments between the adjacent

cells. This holds cardiac muscle cells tightly as the hearth expands and contracts
and is also responsible for contact inhibition. Some of these junctions are present in
narrow bands connecting the neighbouring cells, while others are present in discrete
patches that hold the cells together. This junction is built from the cadherins, which
is a transmembrane protein. The extracellular segment binds to each other, while
the intracellular segments bind to catenins and this in turn bind to actin filaments.

Gap junctions provide hollow intracellular channels of about 1.5-2 nm in diameter to

permit the passage of ions and small molecules between the adjacent cells. The
gap junction does not seal the membrane together as tight junction nor do they
restrict the entry of molecules between the membranes. This junction is composed
of array of channels, which permit the small water-soluble molecules to shuttle from
one cell to another. In addition, this will allow the electrical and metabolic coupling
among cells. Electrical coupling is abundant in cardiac and smooth muscle cells.
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NPTEL – Biotechnology – Tissue Engineering

Depolarization of one group of muscle cell rapidly spreads to the adjacent cells,
leading to the well co-ordinated contractions of those muscles. In case of metabolic
coupling, many hormones act by elevating the intracellular concentration of
secondary messengers such as cyclic AMP. This cAMP can readily pass through
the gap junctions. Hexagonal tubes called connexons connect the two membranes
of the adjacent cells. This connexons is constructed from 4 to 6 copies of
transmembrane proteins called connexins. Orientation of connexins can form a pore
across the gap. However, elevated intracellular calcium and low intracellular pH
established the specific stimuli for closing the connexions rapidly.

Fig 2: Types of cell-cell junctions

Desmosomes provide strong structures involved in the intercellular adhesion. This

exists as a disc shaped structure on either side of the opposing cytoplasmic
membrane. This disc can connect to inside of the own cell via intermediate filaments.
This desmosome connect the cytoplasm of two cells and convey the stresses on one
cell to its neighbours.

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Molecular components in cell junctions mainly are membrane bound receptors

involved in cell adhesion. They are cadherins, Ig super family, cell adhesion
molecule (CAM), selectins and integrins. Cadherins facilitate the adhesion via
homophilic binding to other cadherins in a calcium dependent manner. This appears
to be critical in segregating the embryonic cells into the tissues. This can anchor the
cells through cytoplasmic actin in case of adheres junctions, whereas intermediate
filament in case of desmosomes.

Immunoglobulin like adhesion molecule can function by both homo and heterophilic
binding. Integrins is a group of heterodimeric glycoprotein, both alpha and beta
subunits participate in the adhesion. This will facilitate the cell-ECM interaction. This
exists in both active and inactive states. Selectins expressed only on the leucocytes
and endothelial cells. Like integrins, they are so much important in many host
defence mechanisms. This will bind to the carbohydrate ligands on the cells. Hence
the binding forces are relatively weak.

Molecules involved in direct cell-cell contact are known as cell junction molecules.
This junction may on the order of 1.5 nm diameter and allow the molecules less than
1000 Da to pass through. Assume that the molecules being exchanged never leave
the cells and their size is limited by the diameter of pore. Consider the flux through a
hole on a flat wall. The maximum flux J is calculated as follows:

where D is the diffusion coefficient; d is the diameter of the hole; [C]1 is the solute
concentration in the signalling cell and [C]2 is the concentration in the receiving cell.
When we substitute in typical numerical values such as d= 4 nm; D = 10-5 cm2/sec;
[C]1-[C]2 = 100 µM, we obtain a flux of 2.4 x 105 molecules/pore/sec. Therefore for
100 pores, we obtain a flux of 2.4 x 107 molecules/ sec.

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